Traditionally, the goal of therapy in chronic lymphocytic leukemia (CLL) has been palliative, with first-line therapy using alkylating agents and/or involved field radiotherapy (depending on the stage of disease and sites of involvement) because of the older age of affected patients and the low rate of complete remissions (CRs) with no improvement in overall survival despite treatment. With increasing knowledge about the biology, molecular genetics, and prognostic factors of the disease, the philosophy of care for patients with CLL has evolved from palliation to aiming for a potential cure, especially in younger patients. Furthermore, multiple treatment options have emerged, including purine analogues, monoclonal antibodies, and potentially stem cell transplantation. These have been associated with higher frequencies of CRs and longer durations of responses compared to conventional chemotherapy. In addition, a subset of patients treated with chemoimmunotherapy can achieve durable CRs and molecular remissions. This may translate into improved disease-free survival and potentially a "cure." Because of the heterogeneous nature of CLL, new prognostic markers are currently being incorporated into clinical trials to determine their role in routine clinical practice. This review summarizes current therapeutic regimens that are being evaluated in patients with CLL and management of disease-related complications.