The immune system is conventionally viewed as a means to fight infection. It has become clear, however, that what is considered the “immune” system has also evolved to maintain homeostasis and regulate commensal microbes that normally inhabit the body. Such varied functions demand nuanced and context-appropriate control of immune responses. The thoughts on how immunity becomes activated include two views: by recognition of “nonself” molecules of infectious agents or by recognition of “danger” signals—host molecules released by damaged host cells . Empirical evidence supports both models, but also reveals their limits. Insights from recent studies on insect immune systems, which are generalizable to vertebrates, suggest that the two models may be compatible. That is, a host determines the balance of nonself elicitors and danger signals to decide when to activate the immune system against pathogenic infection while also maintaining healthy relationships with commensals.