Interleukin-23 (IL-23) is a pleiotropic cytokine that maintains the delicate balance between tolerance to commensal microbiota and defense against pathogens at mucosal barriers. When dysregulated, IL-23 becomes a key driver of chronic inflammation, with therapeutics blocking this pathway being successfully harnessed in the clinic. In this review, we discuss recently uncovered biology of IL-23 in the context of mucosal immunity, which intimately links the role of this pathway to the pathophysiology of autoimmunity, chronic inflammation, and emerging functions in cancer. Through the lens of the cell types that respond to IL-23, the engaged effector programs, and the key functions in health and disease, we highlight recent advances and opportunities to better understand the dichotomous outcomes mediated by this cytokine.