The Friend of GATA (FOG) family of proteins is an evolutionarily conserved class of large multitype zinc finger cofactors that bind to the amino zinc finger of GATA transcription factors and modulate their activity. Two FOG genes have been identified in mammals, both of which interact with each of the six known vertebrate GATA factors in vitro. Physical interaction between FOG and GATA proteins in vivo is essential for the development of a broad array of tissues, reflecting the overlapping expression patterns of these factors. In this review, we will discuss the identification and characterization of FOG proteins, their role in human disease, and recent studies that shed new light on their function and regulation.