Targeting IL-17 has become an important option in the current treatment of spondyloarthritis (SpA). To place this therapeutic advancement in context, we review the discovery and properties of this cytokine, noting those which predispose to inflammation and led to it being considered as an attractive target for the treatment of arthritis, especially SpA. The processes that regulate the differentiation of IL-17-producing cells, particularly Th17 CD4+ T cells, have been investigated thoroughly, including the role of IL-23, as these point to additional potential therapies as alternatives to direct IL-17 blockade. IL-17 is a critical cytokine in combatting infection, particularly caused by fungi, but it also has an important role in maintaining epithelial barrier functions, especially in the gut. Both these functions help predict possible adverse effects of IL-17 blockade. Finally, we review the current evidence for the use of IL-17 blockade in various forms of SpA and briefly speculate on future developments.