T-helper 17 (Th17) cells are a new lineage of CD4(+) T cells that are characterized by their production of interleukin-17A (IL-17A). Recent studies show that these cells can also express IL-17F, IL-22, and IL-21. IL-17A and IL-17F can form a heterodimeric cytokine, which mediates biological activities, at least in part, through shared receptors with IL-17A and IL-17F homodimers. The cytokines made by Th17 cells represent three distinct gene families, highlighting the unique biology of these cells. Accumulating data support a role for Th17 cells and these cytokines in inflammatory processes and in animal models of autoimmunity or inflammation. Emerging data in clinical trials support our understanding of the importance of Th17 cells in inflammatory disease. Future clinical studies will allow us to evaluate the role of each cytokine independently in contributing to human diseases with immune-mediated pathologies and to design optimal cytokine-targeted therapies for these diseases.