Set in London, England, good Samaritan Dan Wolf (Jude Law), a struggling writer, takes Alice Ayres (Natalie Portman), a shady young woman and part-time stripper, to the hospital when she's hit by a car, and they fall in love. One year later, Dan meets photographer Anna Cameron (Julie Roberts) and tries to pick her up, but she rebuffs him. In revenge, Dan sets Anna up for an embarrassing encounter with sex-addicted dermatologist Larry Bagley (Clive Owen), but the two end up seeing each other. Then another year later, Dan and Anna begin an affair of their own, and relationships between the four collapse. Over the next year, all of them become obsessed with hurting each other and wreak some heavy emotional damage.

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