The participation of natural killer (NK) cells in multiple aspects of innate and adaptive immune responses is supported by the wide array of stimulatory and inhibitory receptors they bear. Here we review the receptor-ligand interactions and subsequent signaling events that culminate in NK effector responses. Whereas some receptor-ligand interactions result in activation of both NK cytotoxicity and cytokine production, others have more subtle effects, selectively activating only one pathway or having distinct context-dependent effects. Recent approaches offer ways to unravel how the integration of complex signaling networks directs the NK response.