The RUNX family of transcriptional regulators are well conserved throughout the animal kingdom, from the simple nematode worm Caenorhabditis elegans to vertebrates. Interest in the RUNX genes emerged principally as a result of the finding that chromosomal translocations disrupting RUNX protein function are observed in a large number of patients suffering with acute myeloid leukemia (AML). In the 20 years that RUNX genes have been under investigation, they have emerged as central players in the control of developmental decisions between proliferation and differentiation in a wide variety of biological situations. This review focuses on recent data highlighting the roles of RUNX genes in stem cells and illustrates the diversity of processes in which the RUNX proteins play a critical role. In particular, we focus on the role of RUNX1 in hematopoietic stem cells (HSCs) and hair follicle stem cells (HFSCs) and the importance of the solo C. elegans RUNX factor
rnt-1 in stem cell proliferation in the worm. Observations in a variety of stem cell systems have developed to the point where useful comparisons can be made, from which guiding principles may emerge.