The film explores the musical careers of blues musicians Skip James, Blind Willie Johnson and J. B. Lenoir.

Director Martin Scorsese pays homage to the Delta blues. Musician Corey Harris travels through Mississippi and on to West Africa, exploring the roots of the music. The film celebrates the early Delta bluesmen through original performances (including Willie King, Taj Mahal, Otha Turner, and Ali Farka Toure) and rare archival footage (featuring Son House, Muddy Waters, and John Lee Hooker).

The film features interviews and live performances of piano players Ray Charles, Dave Brubeck, Dr. John and Marcia Ball. Eastwood interviews artists as Ray Charles, Dr. John, Marcia Ball, Pinetop Perkins, Dave Brubeck, Jay McShann, Henry Gray and shows archival performances of Fats Domino, Otis Spann, Art Tatum, Albert Simmons, Pete Johnson, Jay McShann, Big Joe Turner, Nat King Cole, Martha Davis, Professor Longhair, Charles Brown and Duke Ellington. Remarkable are two early performances of the Chess Records houseband with Otis Spann, Willie Dixon and, probably, Fred Below.

Director Mike Figgis joins musicians such as Van Morrison, Eric Clapton, Jeff Beck, and Tom Jones, performing and talking about the music of the early sixties British invasion that reintroduced the blues sound to America.

The film follows the career of Blues musician B.B. King. It features performances by B.B. King, Bobby Rush, Rosco Gordon and Ike Turner, as well as historical footage of Howlin' Wolf and Rufus Thomas.

Director Marc Levin travels to Chicago with hip-hop legend Chuck D (of Public Enemy) and Marshall Chess (son of Leonard Chess and heir to the Chess Records legacy) to explore the heyday of Chicago blues as they unite to produce an album that seeks to bring veteran blues players together with contemporary hip hop musicians. Along with never-before-seen archival footage of Howlin' Wolf, Muddy Waters and the Paul Butterfield Blues Band, are original performances by Koko Taylor, Otis Rush, Magic Slim, Ike Turner, and Sam Lay.

Director Charles Burnett presents a tale about a young boy's encounter with his family in Mississippi in the 1950s, and intergenerational tensions between the heavenly strains of gospel and the devilish moans of the blues.