Hematopoiesis is the generation, proliferation and differentiation of hematopoietic stem cells (HSCs) into the erythroid, myeloid and lymphoid lineages. The HSC is a ventral mesodermal derivative that arises due to inductive and patterning processes triggered by bone morphogenetic protein 4 (BMP-4). Recent studies in Xenopus laevis have identified families of transcription factors that participate in hematopoietic development. Transcription factor families, such as the SMADs, Mixs and Vents pattern mesoderm to a ventral fate which ultimately results in the expression of hematopoietic-specific transcription factors such as GATA-1 and SCL. This transcriptional regulatory network enforces the correct temporal and spatial expression of the blood program.