Chronic lymphocytic leukemia is the most common leukemia in the Western Hemisphere and will increase in prevalence as the population continues to age. Partly because of the advanced age of patients and the often prolonged indolent course of disease, therapy has changed little over the past several decades. The clinical course is highly variable and several clinical features have prognostic value. Until recently, therapeutic approaches have ranged from watchful observation to palliative treatment with an alkylating agent alone or combined with a corticosteroid; however, a number of new chemotherapeutic agents (eg, fludarabine, deoxycoformycin, and chloride-oxyadenosine) have been shown to act effectively against the disease. The availability of effective new agents combined with a better understanding of the biology and prognostic determinants in this disease have sparked recent interest in the optimal management of patients with this increasingly common malignancy.