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Despite seminal contributions provided by in vitro studies to the field of hematopoiesis, our present knowledge of mammalian lymphohemopoiesis and the mechanisms governing differentiation and self-renewal of hematopoietic stem cells has been derived in most part from elegant in vivo studies. The inability to apply such an approach to the examination of the human hematopoietic system is the primary reason why several aspects of human hematopoiesis including human stem cell biology are still poorly understood. To overcome the inability to probe human hematopoiesis in vivo, researchers have "humanized" animals via the transplantation of human hematopoietic progenitor cells and other tissues in an attempt to create human-animal chimera suitable for investigating human lymphohematopoiesis in vivo. To date, several of these "humanized" animal models have been developed. During their relatively short existence, human-animal models have contributed substantially to the field of experimental hematology. The development, peculiarities, shortcomings, and applications of these animal models as well as their potential use in exploring the field of human lymphohematopoiesis are the focus of this review.