The past two decades have witnessed significant advances in our understanding of the cellular physiology and molecular regulation of hematopoiesis. At the heart of stem cell self-renewal and lineage commitment decisions lies the relative expression levels of lineage-specific transcription factors. The expression of these transcription factors in early stem cells may be promiscuous and fluctuate, but ultimately comes under the influence of extracellular regulatory signals in the form of hematopoietic cytokines. In this review, we first summarize our current understanding of the phenotypic characterization of hematopoietic stem cells. Next, we describe key known transcription factors which govern stem cell self-renewal and lineage commitment decisions. Finally, we review data concerning the role of specific cytokines in influencing these decisions. From this review, a picture emerges in which stem cell fate decisions are governed by the integrated effects of intrinsic transcription factors and external signaling pathways initiated by regulatory cytokines.