Chronic lymphocytic leukemia (CLL) is typically an indolent B-cell malignancy, primarily affecting the aging population. Standard cytotoxic treatment with alkylating agents or purine analogs is very effective at inducing remission. However, curative treatment is not yet available. Immunotherapy is emerging as an exciting modality with significant potential to advance the treatment of this disease. This review discusses the different modalities of immunotherapy under investigation for the treatment of CLL. These modalities include passive immunotherapy with monoclonal antibodies against antigens on CLL B-cells including CD52 and CD20. Active immunotherapy by vaccination with genetically modified autologous leukemia cells is being evaluated in clinical trials. Allogeneic stem cell transplant for adoptive immunotherapy of CLL is yet another modality being investigated. While this modality may have limited application due to morbidity in older patients, it may result in improved survival and possibly cure. The use of immunotherapy in CLL is in the early stages of development. It is likely that this approach will significantly improve the treatment of CLL and possibly contribute to the cure of this disease.