Our understanding of the role of interleukin (IL)-12 in controlling tuberculosis has expanded because of increased interest in other members of the IL-12 family of cytokines. Recent data show that IL-12, IL-23 and IL-27 have specific roles in the initiation, expansion and control of the cellular response to tuberculosis. Specifically, IL-12, and to a lesser degree IL-23, generates protective cellular responses and promotes survival, whereas IL-27 moderates the inflammatory response and is required for long-term survival. Paradoxically, IL-27 also limits bacterial control, suggesting that a balance between bacterial killing and tissue damage is required for survival. Understanding the balance between IL-12, IL-23 and IL-27 is crucial to the development of immune intervention in tuberculosis.