佩吉和里奥是新婚夫妇，两个人都是艺术家，居住在芝加哥，并且疯狂地爱着对方。在一个雪夜，意外发生了，他们停在路口的车被一辆货车撞了。里奥死里逃生，但是佩吉却陷入了昏迷之中。当她苏醒之后，里奥已经变成了一个陌生人，她失去了五年的记忆。里奥顿时发现自己处在一个非常痛苦的位置上：自己的妻子不认识他，他们之间的爱情自然也荡然无存，而他要重新花时间把这一切重头来过。佩吉所认识的里奥，那个时候她还是一个法律系的学生，随后才转变成的一个艺术家。对于里奥来说，佩吉就是这么一个人，他也不知道此前发生了什么。因为失忆佩吉并不能完全理解自己和父母关系紧张的原因，她也无法明白自己从学校退学，放弃法律专业的根源。更糟糕的是佩吉认为一个叫做杰瑞米的商人依然在追求她，如果按照五年的一切，她根本不会爱上这个在法律上已经是她丈夫的、做音乐的里奥。看上去佩吉的记忆是没有可能恢复了，里奥也不得不面对要失去爱人和爱情这个残酷的现实。但是不准备放弃的里奥决定要重头开始，从他们第一次见面的地方开始。他认为既然能相爱一次，那么为什么不能相爱第二次。 影片改编自真实的故事。
The movie begins with Paige Collins (Rachel McAdams) and her husband Leo (Channing Tatum) coming out of a movie theater. On their way home, when they stop at a stop sign, Paige unbuckles her seatbelt to lean over and kiss Leo. At that very moment, a truck rams their Saab 900 from behind and Paige crashes out through the windshield. Both of them are rushed to the emergency room, and as Leo, in a voice-over talks about how "moments of impact.. help in finding who we are" the movie cuts to how Paige and Leo first met. The scenes of how they courted, proposed and married are interwound with the present.
When Paige regains her consciousness, she thinks Leo is her doctor, implying her loss of memory. Paige verifies what her remaining memories are when she starts a conversation with Leo. She learns she has not lost all, except for the past few years of her life given she still remembers that she wanted to be an artist in high school. Paige is unable to figure out why she left law school.
Later her parents learn about the accident and come to visit her and it is for the first time that Leo meets them. They learn that the doctor recommends she return to her normal routine but her parents and Leo disagree about what her normal routine is at the present time. Leo tells Paige that she stopped talking to her parents before the accident mostly because her father insisted she attend law school while she attend art school. Paige is unable to understand why she broke off the engagement with Jeremy. Leo tries to persuade her to return home with him but she asks for proof such as a diary. He confirms that he does not know of such a diary existing before the accident.
Her parents insist on taking her home with them and Paige agrees assuming she might have married Leo for some mutual benefit. Just as she's about to leave, Leo comes running to play her a voice message in which she sounds very happy and romantic. Paige decides to go back with Leo hoping it will help her regain her lost memory.
On the drive to their home, Paige learns from Leo that the American president is Obama. She recognizes him as the senator. Leo states that she voted for him.
Paige is welcomed home with a surprise party by her friends but as she's not able to remember any of them, she finds it overwhelming and isolates herself from the party. She expresses her anger at the situation to Leo after the party is over and everyone leaves their home. Paige asks him to leave her alone so he complies with her request. The next day Paige appears dressed in a Chicago Cubs hoodie and she says it's the only piece of clothing she owns that she feels comfortable putting on that morning. Leo informs her that it is actually owned by him. She grabs a piece of bacon and she puts it in her mouth but he informs her that she is vegetarian.
Paige reassures Leo that she is fine and she tells him to go to his job. He reluctantly accepts her advice and he leaves her alone at home. Paige continues to eat the bacon once he has left for work.
Paige discovers more evidence of her marriage with Leo while she is alone at home. These come in the form of a video recording of her wedding. She spots the Cafe Mnemonic menu in her hand while she is watching the video.
Paige ventures out to Cafe Mnemonic but does not remember being there and loses her way back. She calls up her mom as she does not know or remember Leo's number.
That evening Leo and Paige are invited for dinner by her parents. Paige's mom brings out filet mignon and she announces it is Paige's favourite dish. Paige accepts it happily despite Leo's puzzled expression.
At the dinner and in the bar later, Leo does not fit in with her family and friends. Leo keeps trying to help her regain her memory but Paige is more drawn towards finding answers as to why she left law school or broke the engagement. And, in one such occasion with Jeremy, she kisses him.
