Major advances have been made in our understanding of the biology and opportunities for treatment of chronic lymphocytic leukemia in recent times. Newer treatment regimens incorporating purine nucleoside analogs have increased the rate of successful remission induction in chronic lymphocytic leukemia patients. Moreover, recent combination chemoimmunotherapy regimens have produced more frequent complete molecular remissions, and early evidence seems to suggest that this could result in prolonged duration of responses, although this association remains to be clearly demonstrated. This review will summarize recent advances in the biology and the management of chronic lymphocytic leukemia, including prognostic factors, pointing mainly on combination chemotherapy based on nucleoside analogs and monoclonal antibodies. In our opinion, in the future a significant improvement of clinical benefits in chronic lymphocytic leukemia will be obtained through the administration of cocktails of monoclonal antibodies combined with chemotherapy in different modalities.