Current therapies for inflammatory and autoimmune diseases include general immuosuppressive agents and newer biologics targeting proinflammatory cytokines. Despite these treatment options, significant unmet medical need remains particularly for more specific targeted agents. Dysregulation of the IL-23/IL-17 pathway is implicated in several inflammatory and autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Accordingly, antibodies targeting IL-23 or IL-17 have shown promise as potential therapies for these diseases. The retinoic acid-related orphan receptor RORγt regulates the expression of IL-17, IL-22, and related cytokines by specialized lymphocytes including subsets of T helper cells, innate lymphoid cells, and γδ T cells. RORγt antagonists represent an alternative approach to target the IL-23/IL-17 pathway and may offer a unique clinical profile from antibodies specific for IL-17.