Significant advances have been achieved in the treatment of acute lymphoblastic leukemia (ALL) with the incorporation of targeted therapy agents. Targeting leukemia surface antigens with monoclonal antibodies is another promising strategy. This article comprehensively reviews available data regarding the use of rituximab for the treatment of Burkitt-type leukemia/lymphoma and CD20-positive precursor B-cell ALL. The incorporation of rituximab into frontline chemotherapy regimens for Burkitt-type leukemia/lymphoma appears to improve outcome. Preliminary data regarding the use of rituximab in frontline therapy for CD20- positive precursor B-cell ALL suggest its use may also be beneficial, particularly for the younger subsets.