Chimeric antigen receptor (CAR) therapy is an emerging immunotherapy that shows great promise for cancer, in particular acute lymphoblastic leukemia (ALL). CARs are recombinant receptors for antigen, which, in a single molecule, redirect the specificity and function of T lymphocytes. Following their genetic transfer to patient T cells, the latter acquire the ability to recognize leukemia cells and destroy them. Several years ago, we identified CD19 as an attractive target for CAR therapy for most B cell malignancies, including ALL. We and others have reported remarkable clinical outcomes in adults and children with ALL, achieving a high complete remission rate irrespective of age, prior treatments, or other prognostic markers. Severe cytokine release may develop in patients with high tumor burdens. Several interventions are available to curb the cytokine release syndrome when it occurs. Based on the impressive results obtained with CD19 CAR therapy for ALL, it is realistic to expect that CD19 CARs will become part of the armamentarium for B cell-ALL and other B cell malignancies.