Natural killer cells are lymphocytes of the innate immune system that can kill an array of tumor and infected cells and secrete cytokines that participate in the shaping of the adaptive immune response. While it was believed that NK cell effector responses are acquired during maturation and then fixed, it appears that the threshold of NK cell responsiveness is more adaptable than originally thought. We review here how the local context provides several signals that impact on NK cell differentiation, responsiveness and shapes the antiviral and immunoregulatory outcome of NK cell activation.