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The treatment of sarcoidosis remains controversial. Corticosteroids remain the cornerstone of therapy, but immunosuppressive, cytotoxic, and immunomodulatory agents have emerged as viable therapeutic options for patients failing or experiencing adverse effects from corticosteroids. Published data are most extensive with methotrexate, but favorable responses have been noted with leflunomide, azathioprine, antimalarial and antimicrobial agents, and tumor necrosis factor-α inhibitors. This review focuses on these novel therapies for sarcoidosis, including indications for use, efficacy, toxicity, and monitoring.