Conventional cytotoxic chemotherapy for adult acute lymphoblastic leukemia (ALL) is not adequate to cure most patients of the disease. Complete remission is achieved in the majority of patients, but responses are often not durable. Allogeneic stem cell transplant is used for patients with high risk features, including those who are positive for minimal residual disease after induction and consolidation therapy. Nevertheless, transplant is a toxic intervention, and does not guarantee long-term disease-free survival. Monoclonal antibodies target surface antigens present on leukemic blasts, with the aim of minimizing off-target toxicity. Rituximab, an antibody directed against CD20, prolongs the survival of younger adults with ALL when added to chemotherapy in the frontline setting. Novel agents, such as the cytotoxin-antibody conjugate inotuzumab, and the bispecific T-cell engaging compound blinatumomab, have exhibited marked antileukemic activity in the relapsed setting. As these agents continue in clinical development, it will be important to eventually incorporate them in the frontline treatment approach. We review current strategies for treating adult ALL, with a focus on novel and targeted therapies that are under development.