He signed a contract to Reprise Records in 1984 to his first album Silverstone.
He released his best-known song in 1990: "Wicked Game" from the album Heart Shaped World and also from the film soundtrack starring from the David Lynch film Wild at Heart and from the 2000 film called The Family Man. The video for the song, directed by Herb Ritts, is also well-known: shot in black and white, it stars Isaak and model Helena Christensen rolling on the beach, holding each other, and whispering in each others' ears.