The currently available different experimental strategies for investigating the biology of the human hematopoietic stem cells are reviewed in this paper. There are discussed: (1) different approaches to isolate human hematopoietic stem cells, (2) available molecular techniques for investigating gene expression in isolated cells, and (3) functional tests evaluating their proliferative potential in in vitro cultures and in vivo in animal models. Important information regarding stem cell biology can be also gained from animal model involving: (1) overexpression of particular genes in transgenic mice or, (2) gene "knock-out" techniques using homologous recombination. The regulation of proliferation and differentiation of human hematopoietic stem cells can be also discerned after downregulation of expression of genes of interest in the early hematopoietic cells using antisense strategy.