Natural killer (NK)-cell receptors specific for major histocompatibility complex (MHC) class I molecules have been identified in humans and mice. Some of the most important receptors are structurally unrelated in the two species: the murine Ly-49 receptors are C-type lectins, while human killer-cell inhibitory receptors (KIRs) belong to the immunoglobulin superfamily. Here, Roland Barten and colleagues describe the divergent and convergent evolution of NK-cell receptors.