Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Although significant advances have been made in the treatment of CLL in the last decade, it remains incurable. Treatments may be too toxic for some elderly patients, who constitute most of the individuals with this disease, and there remain subgroups of patients for which this therapy has minimal activity. This article summarizes the current understanding of the immune defects in CLL. It also examines the potential clinical implications of these findings.