Chimeric antigen receptor (CAR)-modified T cells targeting CD19 expressed by normal and malignant B cells is a unique therapy for patients with chronic lymphocytic leukemia (CLL); recent results highlight the potential of this therapy for patients with relapsed CLL. Because adoptive transfer of CAR-modified T cells is a novel approach, there are issues for the medical oncologist to consider when evaluating current and future clinical trials for CLL patients. This article reviews the impact of CAR design, T-cell production, T-cell dose, conditioning regimens, and tumor burden at the time of CAR-modified T-cell infusion on the efficacy of this therapy.