(hPSCs) for transplantation and disease modeling has been a long-standing goal in the field. In recent years there has been tremendous progress in the field, and investigators have been able to define the developmental cues to direct mesodermal differentiation to definitive HSC fate rather than to embryonic yolk sac-type progenitors. These studies have been largely enabled by the advances in single-cell transcriptomic technologies, permitting comparison of in vitro HSC derivation to human HSCs developing in situ in the embryo. The ability to translate our better appreciation of HSC development in the human embryo into the development of in vitro differentiation protocols has resulted in the generation of multilineage engrafting HSCs (iHSCs) from human induced pluripotent stem cells (iPSCs), a recent and significant advance in the field. In parallel, in recent years, a variety of hPSC models, mainly based on iPSC, have been developed for a variety of non-malignant and malignant blood diseases. These have been shown to recapitulate key disease features both in vitro and in vivo in xenograft assays and have empowered unprecedented interrogation into the pathogenesis and therapeutic targeting of hematologic diseases. Advances in these areas of research will be highlighted in this session.