The discovery of the GATA binding protein (GATA factor) transcription factor family revolutionized hematology. Studies of GATA proteins have yielded vital contributions to our understanding of how hematopoietic stem and progenitor cells develop from precursors, how progenitors generate red blood cells, how hemoglobin synthesis is regulated, and the molecular underpinnings of nonmalignant and malignant hematologic disorders. This thrilling journey began with mechanistic studies on a β-globin enhancer- and promoter-binding factor, GATA-1, the founding member of the GATA family. This work ushered in the cloning of related proteins, GATA-2-6, with distinct and/or overlapping expression patterns. Herein, we discuss how the hematopoietic GATA factors (GATA-1-3) function via a battery of mechanistic permutations, which can be GATA factor subtype, cell type, and locus specific. Understanding this intriguing protein family requires consideration of how the mechanistic permutations are amalgamated into circuits to orchestrate processes of interest to the hematologist and more broadly.