The development of antibody-based therapies for the treatment of both acute and chronic leukemias have undoubtedly been one of the most important advances in the treatment of leukemia. The importance of these novel agents lies not only in their unique mechanisms of action, but also their improved side effect profile which allows patients of advanced age or with significant co-morbid medical conditions to receive potentially beneficial therapies. Advances in therapeutic applications of monoclonal antibodies have come from a greater understanding of the biological characteristics of the antibody, as well as the target antigen, both of which impact the potential efficacy of a particular antibody. In the following review we will discuss the clinical development and potential roles of monoclonal antibodies in the treatment of both acute and chronic leukemias.