Natural Killer (NK) cells boost immune defense via their cytolytic activity and their capacity to produce interferon-gamma. Now Perona-Wright et al. (2009), in this issue of Cell Host & Microbe, show that NK cells can also dampen immune responses to diverse pathogens via secretion of the anti-inflammatory cytokine interleukin-10. Remarkably, this immunosuppressive activity only occurs during systemic infections.