Since the discovery of interferons over 50 years ago, efforts to understand the biochemistry, molecular biology and biological activities of cytokines have been intense and rewarding. Although there are several hundred cytokines and receptors currently recognized, they in fact fall into a fairly limited set of subfamilies (reviewed in [Ozaki K, Leonard WJ. Cytokine and cytokine receptor pleiotropy and redundancy. J Biol Chem 2002;277:29355–58 [1]; Shen F, Gaffen SL. Structure–function relationships in the IL-17 receptor: implications for signal transduction and therapy. Cytokine 2008;41:92–104 [2]). Within these families (and in some cases even outside them), cytokines share many structural and functional features that have provided a framework for understanding their biological activities and signal transduction mechanisms. This review will focus on interleukin (IL)-17, the founding member of the newest subclass of cytokines, which has received considerable attention in the last several years due to its central role in the Th17 system.