Bank loan officer Carl Allen (Jim Carrey) has become withdrawn since his divorce from ex-wife Stephanie. He has an increasingly negative outlook on his life and routinely ignores his friends Pete (Bradley Cooper) and Rooney (Danny Masterson). An old colleague (John Michael Higgins) suggests that he go to a motivational "Yes!" seminar with him, which encourages its attendants to seize the opportunity to say "Yes!". Carl attends and meets inspirational guru Terrence Bundley (Terence Stamp). Bundley publicly forces a reluctant Carl to promise to answer "Yes!" to every opportunity, request, or invitation that presents itself.
Later, Carl says yes to a homeless man's request and is stranded in Elysian Park. Disillusioned, he hikes to a gas station where he meets Allison (Zooey Deschanel), an unorthodox young woman. She gives him a ride back to his car on her scooter and kisses him before leaving. After this positive experience, Carl feels more optimistic about saying yes. However, he refuses oral sex from his elderly neighbor Tillie (Fionnula Flanagan), and then falls down the stairs and is nearly attacked by a dog. Seeing the repercussions of saying no, he goes back to Tillie and to his surprise enjoys the moment.
Carl starts to seize every opportunity that comes his way. He renews his friendships with Pete and Rooney; builds a bond with his boss, Norman; assists Pete's fiancĂŠe, Lucy (Sasha Alexander), with her bridal shower; attends Korean language classes; and much more. He earns a corporate promotion at work and, making use of his guitar lessons, plays Third Eye Blind's song "Jumper" to persuade a man not to commit suicide. Accepting a band flyer outside of a coffee shop, he sees an idiosyncratic band called Munchausen by Proxy; the lead singer is Allison. He is charmed by her quirkiness; she is charmed by his spontaneity and the two begin dating.
Carl and Allison meet at the airport for a spontaneous weekend excursion. Having decided to take the first plane out of town, regardless of its destination, they end up in Lincoln, Nebraska, where they bond more. Allison asks Carl to move in with her and he hesitantly agrees. While checking in for the return flight, Carl and Allison are detained by FBI agents who have profiled him as a potential terrorist because he has taken flying lessons, studied Korean, approved a loan to a fertilizer company, met an Iranian, and bought plane tickets at the last minute. Pete, his attorney, travels to Nebraska to explain Carl's odd habits, lessons, and decisions. As she finds out about Carl's motivational covenant, Allison begins to doubt whether his commitment to her was ever sincere. Deciding that she can no longer trust him, Allison leaves Carl and refuses to return his phone calls.
Carl's life takes a turn for the worse and he almost forgets about Lucy's shower. He manages to arrange a major surprise shower, set his friend Norm up with Soo-Mi (Vivian Bang), a Korean girl, and Rooney with Tillie. After the party, Carl receives a tearful phone call from Stephanie, whose new boyfriend has walked out on her. When Carl goes to Stephanie's apartment to comfort her, she kisses him and asks him to spend the night with her. After Carl emphatically says no, his luck takes a turn for the worse and he decides to end his commitment to the covenant.
Carl goes to the convention center and hides in the backseat of Terrence's convertible so that he can beg to be released from the covenant. Carl emerges as Terrence drives off, and an oncoming vehicle collides with Terrence. The two are taken to a hospital. After Carl recovers consciousness, Terrence tells Carl that there was no covenant. The starting point was merely to open Carl's mind to other possibilities, not to permanently take away his ability to say no if he needed to. Freed from this restraint, Carl finds Allison teaching a sports-photography lesson and admits that he is not ready to move in with her just yet, but that he genuinely loves her, and they reconcile with a kiss as Allison's students take pictures.

Question: What happens when Carl says no to Tillie?
Answer: He falls down the stairs and gets attacked by a dog.
Alternative answer: he falls down steps