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Robert Neville is a scientist who was unable to stop the spread of the terrible virus that was incurable and man-made. Immune, Neville is now the last human survivor in what is left of New York City and perhaps the world. For three years, Neville has faithfully sent out daily radio messages, desperate to find any other survivors who might be out there. But he is not alone.

Irresponsible party girl Maggie is kicked out of her father's and stepmother's home—where she lives for free—and is taken in by her hard-working sister, Philadelphia lawyer Rose. After Maggie's disruptive ways ruin her sister's love life, Rose turns her out as well. But when their grandmother, who they never knew existed, comes into their lives, the sisters face some complicated truths about themselves and their family.