Hematopoiesis is the developmental process by which all blood and immune cells are generated. A decade-old scheme has supported an early and complete separation of the erythro-myeloid from the lymphoid lineages. Recent advances have re-drawn this map, separating lymphoid and myeloid from erythroid programs early in development. Subsequently, the fate restriction of both the lympho-myeloid and the erythro-megakaryocyte progenitors is dependent on Ikaros and its associated chromatin regulators. Genetic studies of this family of nuclear factors are now providing unique insight into the functional molecular signatures that bestow plasticity to the hematopoietic stem cell and its early progeny.