The key role of interleukin-17 (IL-17) and T helper 17 (T_H17) cells in tissue inflammation, autoimmunity and host defence led to the experimental targeting of these molecules in mouse models of diseases as well as in clinical settings. Moreover, the demonstration that IL-17 and T_H17 cells contribute to local and systemic aspects of disease pathogenesis, as well as the finding that the IL-17–T_H17 cell pathway is regulated by IL-23, prompted the identification of inhibitors. These inhibitors include biotechnology products that target IL-23 as well as the leading member of the IL-17 family, IL-17A, and one of its receptors, IL-17 receptor A. Several clinical trials of these inhibitors are underway, and positive results have been obtained in psoriasis, rheumatoid arthritis and ankylosing spondylitis. This Review focuses on the current knowledge of the IL-17–T_H17 cell pathway to better understand the positive as well as potential negative consequences of targeting them.