ABSTRACT: Retinoids are biologic regulators of differentiation, proliferation, apoptosis, and immune response. Retinoids (all-trans retinoic acid, 13-cis-retinoic acid, and the synthetic analogs isotretinoin, etretinate, and acitretin) have been used for years as monotherapy and/or in combination for treatment of cutaneous T-cell lymphomas (CTCL). Orally administered bexarotene, the first synthetic highly selective retinoid X receptor retinoid to be approved by the Food and Drug Administration for CTCL, was shown to be active against the cutaneous manifestations of all stages of CTCL. The topical gel formulation was also effective for early cutaneous manifestations of CTCL or as an adjunct to systemic or phototherapy. Use of retinoids in future long-term clinical trials and their eventual application in CTCL regiments will require strategies to decrease the side effects of existing retinoids, identify novel receptor subtype-selective retinoids with better therapeutic index, and explore biologically based synergistic combination therapies with other active agents.