The therapeutic landscape of chronic lymphocytic leukemia (CLL) is changing rapidly. Advances in the understanding of the biology of the CLL cell and development of new and effective therapies for CLL are starting to shift the treatment paradigm from palliation towards therapy with curative intent. Traditional chemotherapy with alkylators and/or nucleoside analogs achieves complete remissions in up to 30% to 40% of patients. Combinations of monoclonal antibodies with chemotherapy agents (chemo-immunotherapy) have almost doubled clinical complete remissions to 60% to 70%. In addition, eradication of residual disease and achievement of molecular responses have now become possible. New therapeutic agents in development and modifications of stem cell transplant are being evaluated in clinical trials. It is hoped that the combined effort of molecular biology and new therapies will lead to risk-adapted strategies and cure for some patients with CLL.