The conceptual foundation and technical evolution of T-cell genetic engineering for the purpose of retargeting antigen specificity as a clinical immunotherapy modality in oncology have been decades in the making, with many laboratories providing important contributions to overall progress. The development of the component parts of this technology has required the amalgamation of divergent scientific disciplines including cellular immunology, lymphocyte signaling biology, molecular biology, vector virology, and practical improvements in T-cell culture systems. Together with advances in the understanding of clinical variables that facilitate persistent engraftment and expansion of adoptively transferred T cells, the field of CD19CAR research evolved as a logical venue for revealing proof-of-principle clinical antitumor activity. Indeed, the modality has definitively crossed the threshold from a preclinical model system to a therapeutic approach with demonstrable potent antileukemic efficacy in patients harboring advanced and refractory leukemias. The dramatic responses seen in CD19CAR T-cell clinical trials from multiple institutions does not signal an end to the evolution of CD19CAR T cells, as along with early clinical successes, new challenges have emerged that require further refinement of this nascent therapeutic platform.