After hematopoietic cell transplantation (HCT) donor-derived natural killer (NK) cells kill tumor cells to prevent relapse and mediate other beneficial clinical effects including control of infections without inducing graft-vs.-host disease (GVHD). Understanding the determinants of NK cell alloreactivity and function will support improvements in the design of HCT and adoptive cellular therapies. Refinements to the model of NK cell education or licensing have been made which will inform strategies to develop functional alloreactive NK cells for therapeutic use. Differences in NK cell function have been shown to be dependent on the nature of the stimuli. Recent advances have been made in our understanding of the role of activating NK receptors on education and outcome after HCT. The use of adoptively transferred NK cells to treat hematopoietic malignancies has been expanding. New approaches to modulate target sensitivity to NK cell-mediated killing are under development. NK cells play an important role in the therapeutic efficacy of HCT, with effects on control of infections, GVHD, engraftment and relapse prevention. Recent advances in our understanding of NK cell biology will support improvements in our ability to exploit NK cells to treat cancer.