Chronic lymphocytic leukemia (CLL) is the most common adult hematological malignancy in the Western world and predominantly affects the elderly. The disease encompasses a wide spectrum of clinical symptoms, which translate into variable prognosis and survival. The stratification of patients based on their clinical risk profile has been aided by the recognition of novel prognostic markers, for example, VH mutations and ZAP-70 expression, and this process is fundamental to assigning the most appropriate treatment strategy on an individual basis. Although CLL remains incurable with standard treatments, important progress in treatment has been made. The discovery of purine analogs such as fludarabine has led to significant improvements in remission rates and freedom from progression but, unfortunately, no significant prolongation in survival. With the success of newer therapeutic approaches, such as the monoclonal antibodies and stem cell transplantation, the focus of current therapy is on using these approaches in combination with fludarabine to produce high rates of molecular complete response, to eradicate minimal residual disease, and to lengthen survival. This paper provides an overview of CLL and discusses how recent therapeutic developments have changed the management of this form of leukemia.