**Abstract**

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and accounts for approximately 75% of all cases of childhood leukemia. Both diagnostic and therapeutic advances have been instrumental in improving the outcomes of once a dreaded disease. Currently, approximately 90% of the children treated according to risk-directed and response-adapted therapy will be long-term survivors. The use of pediatric protocols for the treatment of adolescent and young adults (AYA) has also resulted in significant improvements in their long-term survival. New therapies including tyrosine kinase inhibitors (TKIs), monoclonal antibodies and CAR T-cell therapy are changing the approach to therapy for relapsed or refractory disease. We are approaching a time where therapy for all patients will be personalized with the use of genome-based characterization of disease and incorporation of drugs against actionable targets, ultimately leading to improved clinical outcomes and decreased toxicity of therapy. Still, certain subgroups including patients with relapsed disease, infant ALL, and those with certain cytogenetic/molecular variants, remain challenging to treat. This chapter is an overview of the recent advances in the ALL disease biology, newly identified prognostic factors and an overview of emerging therapeutic options.

**Keywords:** acute lymphoblastic leukemia, minimal residual disease, CAR T-cell therapy, monoclonal antibody, advances
