Boris Yellnikoff (LARRY DAVID) is a former physicist turned intellectual and grouchy misanthrope who now lives in New York City and has only a handful of friends, such as Joe (MICHAEL McKEAN) and Brockman (CONLETH HILL). His small personal circle is no doubt due to his disdain toward most everything and everyone he comes into contact with, even including the kids who take chess lessons from him.
Accordingly, he doesn't look favorably upon Melody (EVAN RACHEL WOOD), a young woman who's run away from her ultra-religious upbringing in Mississippi and is now outside his building with no place to stay. Although he's obviously reluctant to comply, she convinces him to let her stay with him until she gets a place of her own.
Days turn to weeks and then months, with her adopting his doom and gloom mindset into her otherwise cheery demeanor, and despite yet more reluctance on his part, the two eventually get romantic and then marry. That doesn't sit well with her mom, Marietta (PATRICIA CLARKSON), upon her finally finding Melody, and she quickly sets out to fix her up with aspiring young actor Randy James (HENRY CAVILL).
Likewise, Melody's dad, John (ED BEGLEY JR.), is similarly distressed over the unexpected development, although he, like his estranged wife, ultimately follows Boris' mantra of doing whatever works to make oneself happy, a life philosophy that results in some unlikely personal choices.