Chronic lymphocytic leukemia (CLL) is generally considered to be incurable. It is the most common of the adult leukemias, and many patients are asymptomatic when diagnosed. Most patients survive for several years, and some never require treatment for their disease, leading to the belief that it is an indolent disease. However, this view is changing with the introduction of more effective therapies. Purine nucleoside analogs have become standard in the therapy of most patients. Monoclonal antibodies including alemtuzumab (Campath-IH; Berlex Laboratories, Richmond, CA) and rituximab are playing an increasingly important role in the treatment of patients with advanced disease. Clinical trials will be crucial in defining how and when to treat patients with CLL and will help establish the role of newer prognostic markers and more sensitive methodologies to detect minimal residual disease.