Extracorporeal photoimmunotherapy-photopheresis (ECP) is an immunomodulatory therapy, which basically consists of separating the patient's leucocyte rich plasma from the red blood cell fraction, followed by extracorporeal administration of a photosensitizer and UVA light prior to reinfusion of the treated cells. Successful use of ECP has been reported in patients with cutaneous T cell lymphoma, the Sezary syndrome variant, graft-versus-host disease, cardiac transplant rejection and other T cell mediated/autoimmune and autoimmune diseases. Apoptosis of malignant lymphocytes and presentation of their antigens to anti-tumor CD8+ T cells with induction of an anticlonotypic response by CD8+ effector cells against the CD4+ neoplastic T cells was one of the intial mechanisms of action proposed. The exact mechanism by which ECP exerts its therapeutic effect remains to be further explored and is still uncertain. The better understanding of its mode of action and the clinical benefits of ECP are important findings that provide additional tools to increase the therapeutic armamentarium in a number of acute and chronic T cell mediated diseases.