Advances in the development of monoclonal antibody (MAb) have proven major benefice in the treatment of hematologic malignancies. Phase II studies showed similar results than classical chemotherapy in refractory or relapsed patients, with less toxicity in heavily pre-treated population. Moreover, MAb enhanced sensitivity to chemotherapy. Combined treatments resulted in an increase of global response and complete remission in non previously pre-treated patients with follicular lymphoma, diffuse large cell lymphoma and chronic lymphocytic leukemia. Recently, the association of anti-CD20 and 131Iode was shown to be efficient in follicular lymphomas. The benefits of MAb is less clear in myeloid malignancies. The role of MAb in the treatment of myelodysplastic syndrome remains uncertain although the use of anti-CD33 in acute myeloid leukemias is promising. The aim of this review is to present an updated overview of the most used MAb in the treatment of leukemias and lymphomas not involving bone marrow transplantation.