Although a comparatively recent discovery, induced pluripotent stem cells (iPSCs) have enabled astonishing advancements in numerous fields of study – particularly in the areas of regenerative medicine and personalized disease therapeutics. By returning fully-differentiated adult cells to a pluripotent state, iPSCs capture the unique genetic context of their parental cell source, and have allowed researchers to model diseases affecting hard-to-study tissues, to study the complex three-dimensional arrangement of cell types in organ development, and to develop stem cell-based therapies for conditions ranging from retinal degeneration to diabetes.Stem cell-based therapies have a long history in diseases of the hematopoietic system, where hematopoietic stem cell transplants – most familiarly in the form of bone marrow transplants from healthy donors – have been the standard of care for over forty years, often due to a lack of more targeted therapeutic options because of an incomplete understanding of the complex interactions between genetic aberrations and the development and progression of disease. iPSCs seemed to promise an exciting alternative option for patients, circumventing the current limitations of donor availability and potentially lethal immunological side effects, but thus far the production of transplantable HSCs in vitro from any human pluripotent stem cell source has proven elusive.This dissertation represents a collection of studies utilizing the unique advantages of iPSCs to produce novel insights into both normal and disease-state hematopoietic development, as well as to provide resources for future research. In short, these studies have identified novel miRNA-modulated regulatory pathways enriched in genes differentially-expressed between functional human HSCs and their genetically-matched iPSC-derived counterparts, providing previously unreported insights into recapitulating normal hematopoietic development in vitro. In parallel, these studies have also demonstrated both the therapeutic potential of iPSCs for patients with genetically-driven hematological malignancies by producing karyotypically normal iPSC lines with restored differentiation potential from a patient sample of acute myeloid leukemia (AML), and the utility of iPSCs as a disease modeling resource by producing the first report of a stable iPSC line from the leukemic HL-60 cell line. These findings lay the foundations for future studies to significantly advance our understanding of hematopoietic development and, in turn, aid in the production of novel therapeutic options for patients.