Natural killer (NK) cells are innate lymphocytes involved in immunosurveillance through their cytotoxic activity and their capacity to secrete inflammatory cytokines. NK cell activation is necessary to initiate effector functions and results from a complex series of molecular and cellular events. We review here the signals that trigger NK cells and discuss recent findings showing that, besides antigen-presenting cells, T cells can play a central role in the initiation of NK cell activation in lymph nodes.