During the last five decades, elegant mouse models of hematopoiesis have yielded most of the seminal insights into this complex biological system of self-renewal and lineage commitment. More recent advances in assays to measure human stem and progenitor cells as well as high resolution RNA profiling have revealed that although the basic roadmap of blood development is generally conserved across mammals, evolutionary pressures have generated many differences between the species that have important biological and translational implications. To enhance the utility of the mouse as a model organism, it is more important than ever that research data are presented with regard to how they might be influenced by the species of origin as well as the developmental source of the hematopoietic tissue.