Acute and chronic graft-versus-host disease (GVHD) continue to be the major limitations to successful hematopoietic stem cell transplantation, affecting approximately 30-80 and 60-80% of the patients respectively. A variety of different immunosuppressive and immunomodulating modalities have been tested in both acute and chronic GVHD, among them extracorporeal photopheresis (ECP). ECP involves separation of the patient’s leucocyte-rich plasma, followed by ex vivo administration of a photosensitizer, 8-MOP, and UVA radiation, before reinfusion. It originally started as successfully treatment of cutaneous T-cell lymphoma, and has proved useful effect for a variety of autoimmune diseases and organ transplant rejection, especially cardiac transplant rejection. The procedure induces apoptosis of the irradiated lymphocytes, but the exact mechanism by which ECP exerts its therapeutic effects in these different conditions is uncertain. There is although growing evidence that infusion of apoptotic cells may trigger certain tolerance mechanisms, and of certain interest here is dendritic cells, DCs, which engulf the apoptotic cells. Several studies have reported that ECP induces (via the DCs) a decreased production of pro-inflammatory cytokines, an increased production of anti-inflammatory cytokines, lower ability to stimulate T-cells responses, a shift from Th1 to Th2 cytokine profile, induction of regulatory T-cells and a restoration of the CD4/CD8 ratio in patients with steroid refractory GVHD. ECP has a dose-sparing effect on concurrent immunosuppressive therapy. The treatment has very few adverse effects and is in particular not associated with an increased incidence of opportunistic infections. ECP has been evaluated in small cohort studies of both acute and chronic GVHD, although there is most experience with chronic GVHD, where overall response rates of 50% and higher has been reported in patients with skin, oral, eye, liver, and in some studies lung and gastrointestinal involvement. For the acute form response rates of 60% and higher have been reported for involvement of skin and liver. St. Olavs Hospital in Trondheim is the only hospital that offers ECP in Norway.All these results indicate that extracorporeal photopheresis deserves a place in the treatment of both acute and chronic graft-versus-host disease, and controlled randomised studies are underway to prove the effect compared to conventional treatment.