Chimeric Antigen Receptor (CAR) T cell therapy targeting CD19 has introduced a paradigmatic shift in our treatment approach for advanced B cell malignancies. A major advance has been in the field of pediatric B-ALL where complete responses have been achieved across clinical trials with rates of 65-90% in the relapsed/refractory setting. These striking early response rates led to FDA approval of Tisagenlecleucel, CD19-specific CAR T cells, in August 2017. With broadened access and available longitudinal follow up, it is imperative to study the true durability of CAR-mediated responses and establish long-term relapse free and survival outcomes following CAR therapy. Phase I and II clinical trials have reported event-free survival rates of 50% at 1 year following CD19-CAR infusion in children and young adults with B-ALL. Here, we review some of the major challenges accounting for the discrepancy between early response rates and long term outcomes. In specific, relapse with CD19 or CD19 disease has emerged as a major challenge following CD19-CAR T cell therapy. Related, is the issue of CAR persistence which has been shown to correlate with long-term outcomes. We highlight select efforts to optimize clinical strategies and CAR design to promote enhanced persistence. To date, we do not have robust predictors of response durability and relapse following CAR therapy. The ability to identify patients at risk of relapse in an manner may introduce an interventional window to consolidate CAR-mediated remissions and enhance response durability. This review highlights the need to bridge the gap between the remarkable early complete responses achieved with CD19-CAR T cell therapy and the long-term survival outcomes.