Sézary syndrome is a form of leukemia-lymphoma characterized clinically by erythroderma, pruritus, adenopathy, and circulating atypical cells with cerebriform nuclei. Histologically, atypical lymphocytes in the dermis and Pautrier's microabscesses are often present in skin biopsy specimens. Immunologic findings that support a diagnosis of Sézary syndrome include a predominance of CD4⁺ lymphocytes in both skin biopsy specimens and peripheral blood. Cytogenetic studies that demonstrate aneuploidy and DNA probe analysis that shows gene rearrangement for the β-subunit of the T cell receptor are the latest, most sensitive, and specific methods for identifying the clonal nature of the disease. Various staging systems are used. We review the various treatments for Sézary syndrome, including the newer, biologically based investigational therapies, (e.g., antithymocyte globulin, monoclonal antibodies and other immunostimulants, retinoids, cyclosporine, interferon, and extracorporeal photopheresis). Extracorporeal photopheresis and some chemotherapeutic agents appear to produce the best results in terms of response and remission duration with minimal toxicity. However, more multicenter controlled clinical trials are needed to determine the most effective single or combined therapeutic regimen.