During the past 10 years, significant progress has been achieved in defining new prognostic markers, diagnostic parameters, and treatment options in chronic lymphocytic leukemia (CLL). These developments have led to revision of the National Cancer Institute-sponsored Working Group (NCI-WG) guidelines on CLL established in 1988 and 1996. The update of these guidelines will clarify the role of new prognostic markers in CLL, improve the definitions of response and refractory disease, and add information on the prevention and management of infectious and autoimmune complications.