Initiation of an effective immune response requires close interactions between innate and adaptive immunity. Recent advances in the field of cytokine biology have led to an increased understanding of how myeloid cell-derived factors regulate the immune system to protect the host from infections and prevent tumor development. In this review, we focus on the function of interleukin (IL)-23, a new member of the IL-12 family of regulatory cytokines produced by activated macrophages and dendritic cells. We propose that IL-12 and IL-23 promote two distinct immunological pathways that have separate but complementary functions. IL-12 is required for antimicrobial responses to intracellular pathogens, whereas IL-23 is likely to be important for the recruitment and activation of a range of inflammatory cells that is required for the induction of chronic inflammation and granuloma formation. These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression.