It's a typical day in the life for Mark: he attempts to deal with his zombie roommate, his demonic girlfriend who wants him to meet Daddy, and Homeland Security's efforts to use Mark's client list to meet their quote of illegal immigrant roundups so they can win a ham.
Mark tries to deal with a werewolf integration case, but has more on his hands when Randall can't resist his zombie urges, and Leonard decides to top his brother Christ Angel by performing the ultimate illusion: resurrecting Mark from the dead.
When Mark takes care of an abandoned demon baby, Callie finds herself suffering from strange maternal demon impulses, and Twayne smells her pheromones and grows a mating bone.
Mark accompanies Randall on a trip back to his New Jersey home and meets his roommate's parents... and inadvertently reveals to them that Randall is a zombie. Meanwhile, Leonard tries to find a job for a strange blob creature that can't speak and defies identification.
The city celebrates Treegasm, the mating of Nicky and Neal, treeatures who live in Central Park. However, when Mark encourages Neal to see other trees, things go badly. Meanwhile, Callie needs lots of human sex, and Randall loses his penis.
Frank Grimes blackmails Mark into checking on his daughter's boyfriend, a vampire. Meanwhile, a plague of Mad Larry disease spreads across New York City, transforming hapless citizens into Larry King. And Mark forgets his and Callie's 666th anniversary of their first sex in the bathroom, and Randall is left to pick up the pieces
When the budget for social services is cut, Mark and Leonard find themselves with time off. Mark tries to help Randall, who has been severed at the waist and needs new legs, while counseling a giant ape with OCD. Meanwhile, Callie and Twayne attend a demon convention, and Callie worries that Twayne is hitting on her.
When Leonard has issues that he wants to deal with, Mark steps in to help. Twayne thinks that he has found his soul mate for life.
Mark show his campers at to a team of experts at Camp Friendship when the talent show is only moments away.
Twayne is drafted to be part of Satan's Army and Mark is dragged into joining as well. However, he discovers that there is a plot to destroy humanity. Guest star: Rob Riggle
When Mark finds a magic ring in Leonard's drawer and tries it on, he accidentally activates an engagement that was put away by Leonard at the time when dragons were on the Earth. Randall is taken in to serve as Mark's squire until the married has been "consummated". This leaves for interesting talks.
Callie decides to makes a clone of Mark so that the DOI Bowling Team will win their tournament. But when Clone Mark finds a cruel message in Callie's secret diary, he decides to get revenge by framing her for murder.
Randall puts Mark's soul up for sale on the Soul Exchange, and finds interested buyers in Callie and Aldermach. Meanwhile, Grimes pursues his dream of creating a pop music act with a new teen sensation.
Randall becomes ill after being exposed to a mysterious plant's pollen while attending a party thrown by Twayne on a cruise ship, and Mark may be his only hope to get better.
Callie tells Mark that she hasn't been monogamous, but he'll find out how open-minded she is when his college girlfriend (voice of Jenny Slate) enters the picture.
With Mark working all the time, Randall feels neglected, so he decides that they should spend more time together to decide if they should stay roommates. And Grimes's Mummy (Christine Baranski) returns from the dead, only to find fault with everything Grimes is doing.
A miniature arsonist in Mark's custody escapes up Twayne's nose, forcing Leonard, Grimes and Mark to make themselves smaller for a manhunt inside Twayne's body.
Randall's powerful new arm gets him a job at the Department of Integration, which needs a ringer for a big intramural football game; and the move could send Mark to the second string.
Twayne is roasted by his colleagues for his 10th anniversary at the D.O.I., but Mark's inappropriate remarks cause the man of the hour to resign, putting Mark in charge in a management shake-up that results in the near-destruction of New York City.
Callie gets a promotion by turning herself into a man, forcing Mark to reassess their relationship, which is tested by a dangerous mission to the underwater city of Atlantis.
Randall gets jealous when Mark befriends a new zombie who followed a beloved pop star's lead in joining the ranks of the living dead.
After he's bitten by a rabid Bat-Boy, Mark becomes a masked crimefighter and battles the catlike leader of New York's underworld with help from his sidekick, Koala Man.
In the Season 2 finale, Mark asks Callie to take their relationship to the next level on April Fools' Day, but it's no joke to her vengeful ex-boyfriend. Meanwhile, Leonard believes he has a winning lottery ticket, but Randall wants a cut of the prize.