Mucocutaneous lesions are the most common manifestation of Behçet disease. These lesions can often become refractory to multiple treatments and present challenges to physicians. In this article, different treatments for mucocutaneous lesions in Behçet disease are reviewed and discussed. Topical or intralesional corticosteroids, oral pentoxifylline, sucralfate, dapsone, colchicine, and systemic low-dose corticosteroids, used either alone or in combination, are safe and having varying evidence for effect in mild to moderate mucocutaneous disease. Azathioprine or methotrexate can be used if the lesions are refractory to the previously mentioned therapies. Tumor necrosis factor (TNF) inhibitors such as infliximab or etanercept should be considered as the next step in the treatment if azathioprine or methotrexate fails. Tacrolimus, cyclosporine, and interferon-alpha-2a should be used generally only if TNF inhibitors have failed as a result of their toxicities.