Understanding the factors that influence T helper 1 (T_H1)- and T_H2-cell responses has been one of the main focuses of immunology for almost 20 years. Whereas the central role of interleukin-12 (IL-12) in the generation of T_H1 cells has long been appreciated, subsequent studies indicated that IL-23 and IL-27, two cytokines that are closely related to IL-12, also regulate T_H1-cell responses. However, as discussed in this article, it is now recognized that the ability of IL-23 to stimulate a unique T-cell subset to produce IL-17 has a dominant role in autoimmune inflammation. By contrast, IL-27 has a role in limiting the intensity and duration of adaptive immune responses.