House and the team battle to save a successful, independent blind man who is struck down by a mysterious illness, just prior to him asking for his girlfriend's hand in marriage. Meanwhile, House's mother unexpectedly arrives at Princeton Plainsboro to inform him of her new beau.
A man well-respected in his community suddenly collapses, and in the process of diagnosing his symptoms, the team discovers that the patient has been hiding dark and dishonest secrets about his personal and professional life. But when the patient openly confesses his wrongdoings to his family and community, he compromises his chances of receiving the proper medical treatment. Meanwhile, House will stop at nothing to manipulate Taub into taking a DNA test to prove he is the father of his two six-month-old daughters.
A teenage boy attempting to follow in his late father’s footsteps as an entertainer is admitted to Princeton Plainsboro with partial paralysis. As the team searches for a bone marrow match, they uncover a disturbing family secret. Meanwhile, House looks for creative ways to remove his ankle monitor so that he can attend a boxing match in Atlantic City, and he treats a patient who is convinced he is suffering from diabetes. Also, Taub faces a tough decision when his ex-wife Rachel tells him that she wants to move across the country with their infant daughter.
Over the years, during the course of performing autopsies at Princeton-Plainsboro, Dr. Peter Treiber has often identified mistakes made by physicians that caused the patient's death. These observations have left him questioning the skills of nearly all the doctors on staff... all, that is, except House. When he falls ill, he demands that only House make medical decisions concerning his care. Unfortunately, House and Wilson have taken off on an impromptu road trip without telling anyone, leaving the team to fend alone and lie to their patient to make him believe that House is the guy calling all the shots.
The team takes on the case of Derrick, a 19-year-old college student who had a mysterious nose bleed during cheerleading practice, and discovers that his health issues are likely both physiological and psychological. Possibly suffering from schizophrenia, Derrick claims to hear his deceased brother’s voice in his head. Meanwhile, Foreman tries a different approach with House.
House and the team take on the case of a young boy who has violent dreams of being choked, and then wakes up but still can't take in air. Meanwhile, Park is having intimate dreams involving co-workers, which causes the team to question whether or not there's significance to what each of them dreams. Dominika discovers House has been keeping a secret from her and Wilson drops a bombshell on him.
When House and Wilson disappear off the grid for several days, without explanation, the team is left to deal with a complicated case of a 6-year old with numerous problems and complications, including an overbearing mother who also happens to be her physician.
House and the team take on the case of a man who starts tearing blood. Meanwhile, House is interviewing for a new favorite hooker, since his current favorite, Emily, has decided to get married and leave the business. Desperate for Emily "companionship," House teams up with his "wife" Dominika to sabotage Emily's budding relationship.