Chimeric antigen receptor (CAR) T-cell therapy is transforming the landscape for treatment of B-lineage acute lymphoblastic leukemia (B-ALL). Chimeric antigen receptor T-cell therapy makes use of T cells that have been modified to target a cancer-specific cell surface antigen. There is currently 1 Food and Drug Administration-approved CD19-directed CAR T-cell therapy for relapsed/refractory B-ALL with numerous other CAR T-cell products under clinical investigation. This review covers the development of CAR T cells for B-ALL, citing the remarkable efficacy of inducing remissions in a very high-risk population of patients. However, following the first round of CAR T-cell trials targeting CD19 in B-ALL, it has been found that approximately 50% of patients who initially respond will ultimately recur. Current efforts in the field are focusing on the identification of targets beyond CD19 as well as advancing strategies to promote more durable remissions as work is ongoing to move this therapy upfront.