In this talk I will review the most updated data from trials of CAR-T cell therapy for relapsed or refractory acute lymphoblastic leukemia (ALL), both in the pediatric and adult populations. We will explore some of the most significant challenges in the field: i) the severe, potentially life-threatening, toxicities related to CAR-T cell therapy; ii) the lack of durable responses in a significant proportion of patients. We will discuss the factors driving efficacy and toxicity after CD19 CAR-T cell therapies for ALL, and the role of consolidative allogeneic hematopoietic cell transplantation. Last, I will highlight on-going research aiming at improving outcomes of CAR-T cell therapy for ALL, and offer my take on areas critical for future research.