T-cell large granular lymphocytic (T-LGL) leukemia is characterized by cytopenia and clonal proliferation of large granular lymphocytes. We identified 26 patients with T-LGL leukemia seen at our institution over a period of 8 years. The majority of the patients were asymptomatic at diagnosis. Nine patients were treated with cyclosporine; one achieved a complete remission, and four had a hematological response. Other treatment modalities included single agent alemtuzumab, alemtuzumab combined with pentostatin, fludarabine, and combination of fludarabine and cyclophosphamide. Significant responses were not seen with any of these treatment regimens. We conclude that cyclosporine therapy may be beneficial for T-LGL leukemia patients. New treatment modalities are needed for these patients.