The story centers on Claire Bennett (Jennifer Aniston) a former attorney, as she struggles to come to terms not only with the aftermath of the car accident that killed her son and left her partially disabled by chronic pain, but also with the suicide of Nina Collins (Anna Kendrick), a woman from her chronic pain support group. Nina jumped at the intersection of highways 110 and 105, she landed on a flatbed truck which was hauling used furniture to Mexico ad nobody even discovered her body till it reached Acapulco, which is 2000 miles away. The Mexicans sent her body back in a Rubbermaid cooler, which got stuck in customs and her husband could not even claim her body for a week. Silvana, her housekeeper, caretaker and chauffeur, looks after all of her needs. Claire is full of anger and is kicked off her support group due to her poor behavior. The group leader wanted everyone to look at her and pretend that they are talking to Nina and say their last words to her. Claire refuses to participate in the exercise. She is also separated from her husband Jason Bennett (Chris Messina). Jason has already moved out of the house, and does not even want to see her anymore due to her negativity and bad behavior towards everyone. Claire uses the pool servicing guy to "service" her sexual needs. Claire gives her deceased son's toys to the pool guy, as he has a son of his own. Silvana finds out about this and retrieves all the toys from the pool guy. Claire cannot even properly at night due to her chronic back pain. Claire ends up in her pool to give herself some back support. Claire is supposed to attend the help group meetings and water therapy sessions to demonstrate that she is making an effort, and to continue receiving her pain-killers. So Claire goes to her back pain doctor, and gets them to write the prescription, by distracting them with sweet talk and not letting them check with her primary doctors. It has been 6 months since Claire is taking water therapy sessions with zero improvement, leading the doctors to believe that the problem is not physical. Her water therapist cannot understand why Claire is experiencing so much pain during her sessions. Since the therapy is not having any effect, Claire's medicine prescriptions are cut off. After her water therapy session, Claire jumps into the pool with body weights, seemingly to kill herself. She stays on the bottom for a long time before rising to the surface. As time flies by, with her marriage and life falling apart, she ends up buying drugs on the street to support her addiction. Due to the accident, Claire also has large gashes on her face, which have left a permanent scar. She also dreams vividly and hallucinates about Nina at night when she is trying to sleep. Claire starts visualizing Nina several times leading to short conversations. Silvana (Adriana Barraza), Claire's helper and driver, is very loyal and dutiful. Since the accident, Claire dared not to sit up erect in her car, so Silvana drives her anywhere. As the drug effects diminish, she returns to the present. Claire visits the spot where Nina jumped off the highway intersection to commit suicide. She speaks to a public security person who narrates the sequence of events leading to Nina's jumping off the Highway to her death. By blackmailing Annette (Felicity Huffman) from her ex-support group, and threatening to sue the county for discriminating against her, she procures Nina's address and befriends her husband Roy (Sam Worthington). Roy, having been tipped off by Annette, confronts her as she is leaving. Bonding over their loss and isolation, Claire and Roy go to Nina's grave. A few nights later Claire surprises him at home but takes Nina's leftover Percocet. Claire's dreams of Nina continue. Claire has to travel to Mexico to get her painkillers as her doctor in the US won't give her any. Claire and Roy start getting closer, but Claire pushes him away when he learns about her accident from Silvana and offers her sympathy. But then she is glad when Roy persists and even brings his son over to dinner with Claire. Seeing Roy's son makes Claire confront the loss of her own son in the driving accident. The one day when Claire, Roy and his son are having lunch, a man named Leonard (William H. Macy) comes by to talk to Claire. It turns out that he was the driver of the car that Claire had the accident with. He wants to apologize to Claire, but Claire is incensed. She beats him as hard as she can and asks him to leave her property. Afterwards, she inadvertently overdoses on the pain medication. Taken to the hospital, she dreams of Nina presenting her with a birthday cake with six lit candles, explaining that she feels guilty about not being able to make a homemade birthday cake for her son. Claire is discharged from the hospital and struggles to remain drug free. She asks Silvana to drive her to the drive-in where she had her first date with Jason. Wandering away, she lies down on the nearby railroad tracks and hallucinates a conversation with Nina, who gets Claire to admit she was a good mother. Claire hears Silvana calling her and when she gets up, Nina vanishes. Silvana loudly criticizes Claire for abusing everyone and pushing away Jason, who is also suffering the loss of their son. She is interrupted when Claire notices the car has been stolen, forcing them to stay in a motel. The next day Becky (Britt Robertson), a girl on her way to Los Angeles, tries to steal Claire's purse. Claire brings her home to make her a homemade cake. Silvana later wakes Claire when she sees Becky has in fact stolen the purse but has left a beautiful cake. Claire takes it to Roy for his son's birthday, as a way of thanking Nina. She and Silvana go to visit her son's grave, where Silvana hangs a wind chime in a nearby tree. On the ride home, Claire finally sits upright in the car.
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