ABSTRACT: Photopheresis or extracorporeal photochemotherapy (ECP) is an immunomodulating procedure that has been available for the treatment of cutaneous T-cell lymphoma (CTCL) since 1987. A concentrated white blood cell (WBC) sample spiked with 8-methoxypsoralen (methoxsalen) is exposed to an ultraviolet A light source, then all blood components are returned to the patient. Treatment of mycosis fungoides (MF) and Sézary syndrome (SS) with ECP has been reported in over 400 patients. The combined overall response rate for all stages of CTCL is 55.7% (244 out of 438) with 17.6% (77 out of 438) achieving a complete response. Efficacy in treating certain clinical stages (IB, IIA, III and IVA) and skin stages (T2 and T4) of MF and SS is favorable, although randomized trials comparing ECP to other standard therapies are needed. The use of ECP to treat early stage patients remains controversial. Efforts to establish the effectiveness of combining ECP with other newer immunoadjuvant therapies and modifications of the procedure to enhance immunomodulation are exciting prospects for patients with CTCL.