The outcomes in adult B-cell acute lymphoblastic leukemia (ALL) remain inferior to those achieved in pediatric populations. Targeted therapy with monoclonal antibodies may improve outcomes in adult B-cell ALL without significant additive toxicity. Rituximab is the best known monoclonal antibody and is routinely used in combination chemo-immunotherapy for treatment of adult B-cell ALL and Burkitts leukemia. A number of other monoclonal antibodies are currently under investigation for treatment of adult B-cell ALL including unconjugated antibodies (eg., ofatumumab, alemtuzumab and epratuzumab), antibodies conjugated to cytotoxic agents (eg., inotuzumab ozogamycin and SAR3419), antibodies conjugated to toxins such Pseudomonas or Diptheria toxins (eg., BL22 and moxetumomab pasudotox), and T-cell engaging bi-specific antibodies that redirect cytotoxic T lymphocytes to lyse target ALL cells (eg., blinatumomab). In this article we review the therapeutic implications, current status and results of monoclonal antibody-based therapy in adult B-cell ALL.