Alemtuzumab is a humanized monoclonal antibody specific for CD52, a glycosylphosphatidylinositol-anchored, lymphocyte-surface glycoprotein. Administration of alemtuzumab to patients with chronic lymphocytic leukemia depletes normal and neoplastic lymphocytes from the blood, spleen and marrow, but appears to be less effective in resolving lymphadenopathy. Owing to its activity in clearing leukemia cells of patients who are refractory to purine analogs, such as fludarabine, alemtuzumab became the first and only monoclonal antibody approved by the US FDA and other regulatory authorities for the treatment of chronic lymphocytic leukemia. Here we review the results of clinical studies evaluating the activity and safety of alemtuzumab when used alone or in combination with other antileukemia agents for the treatment of this disease.