Circadian rhythms in physiology and behavior are ultimately regulated at the hypothalamic level by the suprachiasmatic nuclei (SCN). This central oscillator transduces photic information to the cellular clocks in the periphery through the autonomic nervous system and the neuroendocrine system. The fact that these two systems have been shown to modulate leukocyte physiology supports the concept that the circadian component is an important aspect of hypothalamic-immune communication. Circadian disruption has been linked to immune dysregulation, and recent reports suggest that several circadian clock genes, in addition to their time-keeping role, are involved in the immune response. In this overview, we summarize the findings demonstrating that Natural Killer (NK) cell function is under circadian control.