Recent studies have documented that the immunoregulatory functions of IL-12 may play a role in promoting endogenous protective responses during infections and/or contribute to pathology resulting from unregulated cytokine expression. Pathogen induction of IL-12 elicits interferon-γ production by natural killer cells, which contributes to early defense during certain bacterial, parasitic, and viral infections. IL-12 also facilitates the development of T helper type 1 (Th1) lymphocytes required for late protection against bacteria, parasites, and fungi. During viral infections, however, there appear to be mechanisms independent of IL-12 for inducing protective T-cell responses. In contrast, negative regulation of IL-12 during acute infections can be a key event in the establishment of chronic infection and protection against harmful excessive cellular immune response. Under appropriate conditions, IL-12 has therapeutic efficacy for promoting defense against a variety of pathogens, and for use as a vaccine adjuvant to enhance beneficial Th1 over detrimental Th2 lymphocyte responses. This information extends knowledge about the regulation of immune responses to infectious agents, and provides new insights for the development of treatment and adjuvant strategies to potentiate beneficial or inhibit detrimental endogenous immune responses.