The function of natural-killer (NK) cells is modulated by the balance between a number of activating and inhibitory receptors. Killer immunoglobulinlike receptors (KIRs) are mostly inhibitory receptors. They play a critical role in recognizing self-class-I major histocompatibility complex (MHC) molecules and thus protect healthy host cells from NK-targeted lysis. In contrast, both NKG2D and CD16 are activating NK receptors that trigger the NK-cell lysis of various tumor and virally infected cells through either direct ligand engagement or antibody-dependent cellular cytotoxicity (ADCC). Through structural studies of members of these distinct receptor families, in particular, the structure and recognition between KIR2DL2 and HLA-Cw3, that between NKG2D and ULBP3, and that between CD16 and IgG Fc, considerable understandings have been achieved about their function and their ligand recognition.