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Blood cell production or hematopoiesis is one of the most well-understood paradigms of cell differentiation in the body. The majority of work on hematopoiesis comes from studies that have primarily been conducted in mice, zebrafish, or other valuable model systems. However, it is clear that such model organisms may not consistently and faithfully mimic what is observed in humans with blood disorders. Moreover, there is significant divergence between species that is increasingly being appreciated at the genomic level. As a result, there is an opportunity to use observations in humans to provide a refined view of hematopoiesis. Here, we discuss vignettes from our work that illustrate how insight from human genetics can improve our understanding of blood cell production and identify promising therapeutic approaches for blood disorders.