Recent studies have suggested that pediatric-intensive chemotherapy regimens can improve outcomes in adults with acute lymphoblastic leukemia (ALL) up to the age of 45. Above this age, toxicities increase. Monoclonal antibody-based therapies bring the promise of increased response rates without excessive toxicity. The addition of rituximab to combination chemotherapy has shown encouraging results. Newer monoclonal antibody-based therapies linked to cytotoxic agents show promise. These include inotuzumab ozogamicin, an anti-CD22 antibody linked to calicheamicin that has produced significant single-agent responses in relapsed and refractory ALL. Other monoclonal antibodies linked to plant or bacterial toxins are in earlier stages of development. Blinatumomab is a novel bispecific T-cell engaging antibody that combines single chain antibodies to CD19 and CD3 and brings a T cell in close proximity to a leukemic lymphoblast with resulting redirected lysis. This agent has demonstrated encouraging results in both the minimal residual disease setting and the relapsed/refractory setting. Autologous chimeric antigen receptor cells have shown promising responses in indolent B-cell lymphoid malignancies and are being tested in ALL. Many of these agents have the potential to increase response rates in older adults. Trials of many of these monoclonal antibody-based therapies are in various stages of development in the treatment of newly diagnosed ALL.