Barry Egan (Adam Sandler) is a single man who owns a company that markets themed toilet plungers and other novelty items. He has seven overbearing sisters who ridicule and emotionally abuse him regularly and leads a very lonely life punctuated by fits of rage and anguish. In the span of one morning, he witnesses a bizarre car accident, picks up an abandoned harmonium from the street, and encounters Lena Leonard (Emily Watson), a co-worker of his sister, Lena having orchestrated this meeting after seeing him in a family picture belonging to his sister Elizabeth (Mary Lynn Rajskub).
Coping with his loneliness, Barry calls a phone sex hotline, but the female operator attempts to extort money and sends her four henchmen, who are brothers, to collect. This complicates his budding relationship with Lena, as well as his plan to exploit a loophole in a Healthy Choice promotion and amass a million frequent flyer miles by buying large quantities of pudding (based on the true story of David Phillips). After Lena leaves for Hawaii on a business trip, Barry decides to follow her. He arrives and calls one of his manipulative sisters to learn where Lena is staying. When his sister tries manipulating him again, Barry snaps and demands she give him the information, which she does. Lena is unexpectedly overjoyed to see Barry, and they have a pillow talk scene. At first, Barry explains that he is in Hawaii on a business trip by coincidence, but he soon admits that he came to pursue a romantic relationship. The romance further develops, and Barry finally feels some relief from the emotional isolation he has endured.
After they return home, the four brothers ram their car into Barry's, leaving Lena mildly injured. With his newly found freedom from loneliness in jeopardy, a surprisingly aggressive and poised Barry adeptly fights off all four the goons in a matter of seconds. Suspecting that Lena will leave him if she finds out about the phone sex hotline fiasco, Barry leaves Lena at the hospital and tries to end the harassment by calling back the phone-sex line and speaking to the "supervisor", who turns out to be Dean Trumbell (Philip Seymour Hoffman), who is also an owner of a mattress store. Barry travels to the mattress store in Provo, Utah, to confront Dean face to face. Dean, at first trying to intimidate Barry, finds Barry much more intimidating and Barry compels Dean to leave him alone.
Barry decides to tell Lena about his phone-sex fiasco and begs her for forgiveness, pledging his loyalty and to use his frequent-flier miles to accompany her on all future business trips. She readily agrees, and they embrace happily. Lena approaches Barry in his office while he plays the harmonium. She puts her arms around him and says, "So, here we go."