Eddie is bedridden and dying of lung cancer. His wife Charlotte, and their friends and family have gathered at his bedside to say goodbye. Eddie asks them to leave him alone with Charlotte, and he apologizes to her for never taking her to the beach on Rio as he promised. Charlotte assures him that she's always loved him, and Eddie says he's ready. However, Charlotte starts choking as her throat closes up and Eddie manages to get out of bed despite his ailment and call for help.
House arrives in the conference room and discovers Kutner and Thirteen are missing. Taub tells him that Thirteen is with their new patient and Kutner has a sick dog. House suspects he's lying out of guilt because he stole Kutner's diagnosis in their previous case. They go over the files and discover that Charlotte recently took a trip to Hawaii to visit her sister on the beach, but the only thing she might have caught there that accounts for her symptoms would have spread to Eddie. Taub suggests a virus and House agrees authorizes preventative treatment until they have a clearer idea of what Charlotte has. Thirteen arrives to tell them that Charlotte wants to be released. She noticed that Eddie improved when she got sick, and hopes he can recover if he sees her sick. House is indifferent and figures if she wants to die, that's her concern. Taub has another suggestion, and reunited the couple in Charlotte's hospital room.
After a treating a young beauty pageant girl for drunkenness, House gets word that Charlotte is recovering. He still doesn't particularly care, and wonders where Kutner is. However, Charlotte has another respiratory seizure despite the anti-viral treatments.
Foreman and Thirteen go to Kutner's apartment to find where he is. Thirteen has a key and they go in, and find his apartment filled with science fiction posters and toys. Looking around, they find a grisly discovery: Kutner, dead on the floor from a gunshot wound to the head. They try to revive him but it's clear he's been dead for hours.
Back in differential, the team is grief stricken. House starts accusing the others of not noticing anything wrong, and then apologizes. He suspects Kutner panicked over something; Thirteen doesn't believe Kutner ever tried to reach out to them; Foreman blames himself for not seeing any potential signs of suicide. Taub, Kutner's closest friend, insists that committing suicide is stupid and returns to the case. Foreman suggests they pass it on to another doctor but House points out that it won't make Kutner's death okay. Cuddy comes in to offer time off if they want it, but figures no one will accept it. After the differential, Cuddy wonders if House is doing okay. She wonders where Wilson is and House says is friend is giving him space. She expresses her condolences to House, who abruptly tells her he's not the one who suffered a loss. She looks at him with pity and leaves.
While Taub treats Charlotte, House decides to accompany Foreman and thirteen to see Kutner's adopted parents. Taub explains they're going to give her an anti-inflammatory treatment and Eddie tries to get her to relax by getting her to imagine a trip to Rio.
House and the others talk with Julia and Richard, who wonder if they know why Kutner shot himself. House talks about how they forced Kutner to take their name and didn't respect his heritage, and drove him to kill himself. Richard calls him a son of the bitch, but House doesn't relent. Foreman interrupts to tell him to go back to the office. Realizing what he's said, House offers his condolences and leaves.
House returns to the hospital and Taub tells him that Eddie is recovering but Charlotte's condition is getting worse. Taub insists that Kutner didn't want help and there was nothing he could do, and House points out that if Taub hadn't received help, he might be dead now. Having eliminated all other possibilities, House realizes what Charlotte is doing. He goes to her and tells her that they need to induce a heart attack to burn off her excess heart muscle. When Eddie says that's nuts, House admits that he was lying by proposing something so radical that Charlotte would tell the truth. She admits that she was faking because Eddie improved when she did. Charlotte's also happy that Eddie has become more loving toward her since she became ill. Before she can say more, Charlotte clutches at her leg in agony. House thinks she's faking again until Taub checks and discovers that her leg muscles are deteriorating.
As they discuss the case, House admits his theory about Kutner's conflict over his race wasn't the reason he killed himself. With the new symptom, Foreman suggests Charlotte has MS. They prepare to do a MRI test and House orders Taub to check Eddie's heart. House then talks to Cuddy, noting that he was a pervert. Cuddy says it was a college streaking incident and talks about how Kutner was like House so it's natural House would take it badly. House insists that if Kutner were anything like him, he would have realized that living with pain is always better than dying.
As Thirteen runs the MRI on Charlotte, the patient admits that Eddie never was overly affectionate during their 30-year marriage. However, she was happy to have him. Before she can continue, she has another seizure and passes out.
While Taub runs the heart test, Eddie talks about how he never loved Charlotte as much as he could have, but he's hoping that if his cancer is remission then he can have the time to make things right. Taub warns that it's natural Eddie would say that after a life-threatening illness, but harder to actual do. He then tells Eddie that the tests show his heart hasn't improved.
Cuddy goes to see Wilson, who says he has his own problems and can't deal with House's as well. When Cuddy insists, Wilson accuses her of just wanting to make sure her number one doctor is okay. Cuddy insists it's more and tells him that House accused Kutner's parents of driving him to suicide.
The team now believes that Charlotte is suffering from rheumatic arthritis. Chase needs to operate and stabilize her spleen so they can do a biopsy. Taub is watching from the gallery, and Chase wonders why he's there instead of mourning Kutner. Taub explains he'd rather deal with the person who wants to live, and Chase calls him a bastard. As he operates, Chase realizes that Charlotte's condition has spread from her spleen to her liver.
Wilson finds House at Kutner's apartment, trying to figure out why Kutner killed himself. Wilson accuses House of being interested because it's a puzzle, not because he ever cared about Kutner. He suggests they go get drunk, but House concludes there's nothing for him to miss because Kutner didn't kill himself: he was murdered.
Back at the hospital, Foreman takes some time off, and told House rather than his girlfriend Thirteen. Now that Eddie's condition is getting worse again, House isn't interested and tries to work out why Kutner was murdered. Thirteen and Taub both think he's deflecting and refuse to pursue any leads. House then returns to Charlotte's case and orders a test for anti-trypsin deficiency.
Taub runs the test and Charlotte asks to be with Eddie. When he tells her she's in no condition to see him right now, she asks him about the transplant procedure. After he tells her that a volunteer can bypass the organ donation registry, Charlotte tells him that she and Eddie are compatible, and when she dies she wants her heart to go to Eddie.
Thirteen goes to Foreman's apartment. He answers the door and explains that in the past, he's always dealt with tragedies solo. Realizing she's not wanted, Thirteen leaves.
House goes through Kutner's e-mails, and explains to Cuddy that the man who shot Kutner's birth parents is coming up for parole. Cuddy points out that the man is still in prison according to the records. House wonders why she wants him back on Charlotte's case and figures she's doing it so he'll have something to hold onto.
Charlotte collapses to the floor from a seizure, but Taub realizes she tried to kill herself so Eddie could have her heart, literally. Her liver is destroyed in the attempt and she needs a transplant. Without a diagnosis, the transplant committee won't risk a healthy liver donation. House is willing to lie, but Thirteen warns it hasn't worked in the past and Taub observes that Kutner would have said to tell Cuddy the truth.
House goes to see Cameron and wants her to convince Eddie to undergo surgery to donate part of his liver. She realizes that Eddie would die on the table, and they could then give Charlotte his liver. House wants her to try and persuade him because she's big on love. Before she goes, Cameron points out that House wants to believe Kutner was murdered because that lets him off the hook for not realizing his team member was suicidal.
Cameron explains to Eddie what will happen. He agrees but she explains they can't even let him say goodbye to her because it might give away what they're planning. Eddie admits that she'll hate him for dying to save her, but signs the donation papers. Cameron notices he has nodules on his fingers and goes to House, saying they're a new symptom. House doesn't believe it. Worse, he's learned that the killer of Kutner's parents has died in prison so there was no murder involved. Cameron insists that he can give up on Kutner, but he has a living patient that needs his help. House agrees to test and discovers Eddie has a fungal infection that simulated cancer. When he became concerned for his wife, his body chemistry altered, helping him temporarily fight back the infection. They can treat Eddie, but he refuses and insists he wants to die. If they won't let him die, then he'll refuse the treatment, demand they release him, and kill himself so Charlotte can have his liver.
House considers killing Eddie, since that way they can obtain the liver under controlled conditions. Thirteen refuses but Taub agrees, saying they can avoid a second pointless death. However, he reconsiders and wheels Eddie into Charlotte's room, then tells her the plan. Charlotte is angry but before she can answer, she collapses from a fever.
With the new symptom, no possible diagnosis fits given the facts of the case. House realizes that there must be a fact they don't have: someone lied. He confronts Charlotte and points out that Rio has different sand flies than Hawaii. Charlotte breaks down and explains that she went to Rio with a friend, and hid it from Eddie. She was tired of waiting for him to take her to Rio as he had promised. She apologizes to her husband, and House explains that sand flies native to Rio gave her visceral leishmaniasis, which accounts for her symptoms. Now that they have a diagnosis, they can treat her and okay the liver transplant.
Later, Taub informs Cuddy that it's too late: it's too late for the treatment to work and Charlotte will die regardless. She invites him to ride with her to Kutner's funeral, but he says he's staying behind. Cuddy points out that Charlotte's illness gave Eddie enough time for them to diagnose his problem and cure him. Taub isn't satisfied and feels it was just another pointless death, like Kutner's.
Wilson goes to see House, and observes that House's worry is that he's losing his skills because he failed to diagnose Kutner's mental state. He wonders what House will do if he ever believes he's no longer a gifted doctor. House tells him to go to the funeral: he's staying behind.
The rest of the staff go to the funeral, and Thirteen spots Foreman standing in the back. He and Thirteen act as pallbearers.
As Charlotte slips away, Eddie takes her hand and kisses it one more time.
House sifts through Kutner's apartment and tries to find a reason for him killing himself, a reason that House never saw.
Outside the temple, Foreman breaks down and takes Thirteen's hand.
In a hospital corridor, Taub sits down and finally cries for his lost friend.
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