Initially from Galesburg, Illinois Tanning moved to New York in 1935 to work as an illustrator, she discovered Surrealism at the 1936 MoMa exhibition Fantastic Art, Dada and Surrealism.

Tanning's early works are figurative renderings of dream-like situations – paintings such as Birthday and Eine kleine Nachtmusik, with meticulous attention to detail. Many of which combined erotic subjects with enigmatic symbols and desolate space. During the 1950's she began to develop her own unique style - fragmented and prismatic - as in Insomnias(1957). "Around 1955 my canvases literally splintered... I broke the mirror, you might say," she explains. By the late 1960s her work is completely abstract.

Tanning was married to writer Homer Shannon in 1941. In 1942 she met the great love of her life Max Ernst. The two quickly became a New York art-world power couple with many friends, including Henri Cartier-Bresson, Lee Miller, Roland Penrose, Yves Tanguy, Kay Sage, Pavel Tchelitchew, George Balanchine (who she designed ballet sets for), and Dylan Thomas. In 1946 Tanning and Ernst were married in a double wedding with Man Ray and Juliet Browner. They lived together in Sedona, Arizona as well as Paris and Touraine in France until Ernst's death in 1976.

Tanning died at the age of 101 in her Manhattan apartment.

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