MHC class I molecules are ligands for the killer-cell immunoglobulin-like receptors (KIRs), which are expressed by natural killer cells and T cells. The interactions between these molecules contribute to both innate and adaptive immunity. KIRs and MHC class I molecules are encoded by unlinked polymorphic gene families that distinguish all but the most related individuals. Combinations of MHC class I and KIR variants influence resistance to infections, susceptibility to autoimmune diseases and complications of pregnancy, as well as outcome after haematopoietic stem-cell transplantation. Such correlations raise the possibility that interplay between KIR and MHC class I polymorphisms has facilitated human survival in the presence of epidemic infections and has influenced both reproduction and population growth.