Natural killer cells were first described over 40 years ago, but the last 15 years has shown tremendous progress in our understanding of their biology and our ability to manipulate them for clinical therapeutic effect. Despite the increased understanding by clinicians and scientists investigating these cells, their biology remains a confusing subject for many because of the wide array of receptors, complex interactions, multiple models of predicting function, and contradictory data in the literature. While they are microscopically indistinguishable from T cells and share many of the same effector functions, their mechanisms of target recognition are completely distinct from yet complimentary to T cells. In this review we provide a basic understanding of NK cell biology and HLA recognition as compared and contrasted to T cells using a metaphor of border patrol and passports. We conclude with a summary of the evidence for NM cell effects in hematologic malignancies and describe new advances in NM cell immunotherapy aimed at improving these effects. (C) 2016 Elsevier Ltd. All rights reserved.