Extracorporeal photopheresis (ECP) is the first FDA approved cellular photoimmunotherapy for cancer, namely cutaneous T-cell lymphoma, and has demonstrated efficacy in various diseases that have a suspected involvement of pathogenic T-cells including prevention and treatment of acute and chronic graft-versus-host disease, organ transplant rejection, selected autoimmune diseases and Sezary syndrome. In ECP, patient’s blood mononuclear cells are collected, exposed to ultraviolet light in the presence of extracorporeally administered liquid 8-methoxypsoralen and reinfused. Besides its considerable efficacy ECP has an exceptional safety profile, does not cause general immunosuppression and thus, does not increase risk of infectious complications and relapse of malignant disease. Exciting preclinical data and clinical observations provide insight into the mechanisms of action of ECP and support its immunomodulatory role. This book will provide an overview on the historical development of ECP, technical aspects for its use in various patient populations including children and adults, novel research findings both in preclinical models and in various patient cohorts and will stimulate further research in organ, tissue and cell transplantation and autoimmune disorders.