The ultimate goal of developmental immunology is to understand the normal processes that give rise to the immune system in order to diagnose and develop effective treatments for diseases that occur as a consequence of immune system defects. Central to achieving this goal is understanding the complex interplay between microenvironmental signals and transcription factors that direct human hematopoietic differentiation and lineage commitment. The ability to isolate highly purified populations of human hematopoietic cells at critical points in differentiation make it possible to answer very specific questions about the hematopoietic process and lineage restriction. This review describes the use of surface immunophenotypes to identify human hematopoietic cells at particular points in differentiation or with particular patterns of lineage restriction. Culture models are discussed in the context of the ability to detect, characterize and determine the lineage potential of human hematopoietic stem cells and progenitors. Variations in hematopoeises that correspond to ontogeny will be examined. Potential roles for the HOX and Ikaros proteins in human lineage commitment will be considered. Also included will be discussion of a number of factors that provide challenges to experimental design, to experimental interpretation, and to the development of a comprehensive model of human hematopoiesis.