When a decorated Marine goes missing overseas, his black-sheep younger brother cares for his wife and children at home—with consequences that will shake the foundation of the entire family.

Brothers tells the powerful story of two siblings, thirtysomething Captain Sam Cahill (Tobey Maguire) and younger brother Tommy Cahill (Jake Gyllenhaal), who are polar opposites. A Marine about to embark on his fourth tour of duty, Sam is a steadfast family man married to his high school sweetheart, the aptly named Grace (Natalie Portman), with whom he has two young daughters (Bailee Madison, Taylor Grace Geare). Tommy, his charismatic younger brother, is a drifter just out of jail who's always gotten by on wit and charm. He slides easily into his role as family provocateur on his first night out of prison, at Sam's farewell dinner with their parents, Elsie (Mare Winningham) and Hank Cahill (Sam Shepard), a retired Marine.

Shipped out to Afghanistan, Sam is presumed dead when his Black Hawk helicopter is shot down in the mountains. At home in suburbia, the Cahill family suddenly faces a shocking void, and Tommy tries to fill in for his brother by assuming newfound responsibility for himself, Grace, and the children.

But Sam is not dead; he and a fellow soldier have been captured by Taliban fighters. In Afghanistan's harsh, remote Pamir Mountains, Sam is subjected to traumas that threaten to rob him of his very humanity. At the same time that Sam's sense of self is being destroyed overseas, Tommy’s self-image is strengthening at home. And in the grief and strangeness of their new lives, Grace and Tommy are naturally drawn together. Their longstanding frostiness dissolves, but both are frightened and ashamed of the mutual attraction that has replaced it.

When Sam unexpectedly returns to the States, a nervous mood settles over the family. Sam, uncharacteristically withdrawn and volatile, grows suspicious of his brother and his wife. Their familiar roles now nearly reversed, Sam and Tommy end up facing the ultimate physical and mental challenge when they confront each other. In the shifting family dynamics, who will dominate? And how will the brothers come to terms with issues of love, loyalty, and manhood—and with the woman caught between them?