The treatment of adult acute lymphoblastic leukemia (ALL) poses a tremendous challenge for hematologists. The use of pediatric-based chemotherapy regimens in young adults up to the age of 45 years has resulted in improved outcomes when compared retrospectively with historical controls treated with adult therapy. A better understanding of the molecular landscape of ALL and advances in the field of monoclonal antibody therapy have resulted in the development of several new agents that may provide for a reduction in the toxicity inherent in pediatric-like regimens. The anti-CD20 antibody, rituximab, anti CD22 antibody, epratuzumab, anti-CD22 antibody-drug conjugate, Inotuzumab ozogamicin, the bi-specific T-cell engager (BiTE) antibody, Blinatumomab, and chimeric receptor antigen (CAR) therapy are among the emerging agents that have demonstrated the potential to improve response rate and decrease toxicity when used alone or in combination with chemotherapy. Several role-defining phase II and phase III clinical trials with these agents are currently underway in the relapsed/refractory and newly diagnosed ALL settings.