Purpose of Review <p> Extracorporeal photopheresis (ECP) is an immunomodulatory treatment in which an apheresis machine isolates mononuclear cells from whole blood that are then treated with psoralen and ultraviolet-A light and reinfused into the patient. ECP has been approved for use in cutaneous T-cell lymphoma (CTCL) for 30 years; it has also been shown to be effective for graft-versus-host disease, solid organ transplant rejection, and various autoimmune diseases. Nonetheless, ECP is relatively underutilized, perhaps due to knowledge gaps and resource limitations. Here, we review ECP indications and techniques, as well as the data supporting its use in clinical settings. </p> Recent Finding <p> Recent clinical studies have emphasized the durability of ECP in CTCL, both as monotherapy and in combination with topical and other systemic CTCL treatment modalities. New insights into the mechanism of action underlying ECP have illuminated its effects on both cellular and humoral immunity. Specific clinical and laboratory findings have been identified as potential predictors of ECP response. </p> Summary <p> ECP is a well-tolerated and effective treatment option for a growing list of indications. In CTCL, ECP can achieve durable responses with longer treatment courses and should be considered as a first-line option for erythrodermic disease and Sézary syndrome. </p>