Mycosis fungoides, the most common form of cutaneous T-cell lymphoma, is a helper/memory epidermotrophic T-cell lymphoma presenting as skin lesions. At the current time, curative therapy does not exist, and many patients have chronic skin lesions for many years, with successful treatment limited to the skin. Mycosis fungoides appears to start as a human lymphocyte antigen-restricted immune response, which may be antigen or superantigen driven, in early stages. From a dermatologist's perspective, removing the stimulating antigen(s), treating infections, preserving the skin barrier, targeting the abnormal clone, preserving the cytotoxic response, and using skin-directed therapy early in the disease are sensible strategies. As the disease progresses to involve more of the skin surface, systemic therapies, especially biological response modifiers (interferon and retinoids), phototherapy, or photopheresis help to preserve the patient's innate immunity and are widely used. New agents including bexarotene (a rexinoid) and DAB(389)IL-2 (interleukin-2 diphtheria fusion protein) offer new therapeutic options that are advantageous for treatment of mycosis fungoides in later stages.