The past 20 years have witnessed a revolution in our understanding of platelet alloimmunity, both in terms of basic findings and clinical applications. This review highlights recent molecular biological studies that have impacted our understanding of the structural basis for the formation of human platelet alloantigenic epitopes, and shows how these findings have improved methods for their detection and genotypic analysis. Finally, implications for dissecting the way in which the immune system both recognizes and responds to platelet alloantigens are discussed.