The contribution of Th17 cells to the development of colitis is well described. The effector cytokines IL-17A and IL-17F have been proposed as potential therapeutic targets for the treatment of patients with inflammatory bowel disease. In a proof-of-concept study for the treatment of patients with Crohn's disease, secukinumab, a monoclonal antibody directed against IL-17A, was ineffective and associated with more adverse events than placebo. Wedebye Schmidt et al. propose that blockade of both IL-17A and IL-17F, rather than either cytokine alone, attenuates the development of colitis in a T-cell transfer model of experimental colitis. These findings suggest that combined blockade of IL-17A and IL-17F may be an effective strategy for the treatment of patients with inflammatory bowel disease.