The core binding factors are a small family of transcription factors comprising a DNA binding CBFα subunit and a non-DNA binding CBFβ subunit. One gene encoding a CBFα subunit, RUNX1 (also known as AML1, CBFA2, and PEBPA2A), and the gene encoding CBFβ (CBFB) are essential for hematopoiesis and are frequently mutated in human leukemias. Both genes are required for the generation of hematopoietic stem cells (HSCs) during embryonic development. Expression studies in fish and frogs and functional analyses in flies indicate that a role for these genes in hematopoiesis is evolutionarily conserved.