The success of rituximab, the first monoclonal antibody ever licensed for the treatment of a human malignancy, has not only increased survival and cure rates in many non-Hodgkin lymphomas of the B-cell type, but has prompted an explosion in the development of novel antibodies and biologically active substances with specific cellular targets ("targeted therapy") both in the field of hematological malignancies and solid tumors. The chimeric anti-CD20 monoclonal antibody rituximab is the first drug that was shown to increase overall survival in follicular lymphomas and to cut lymphoma-associated deaths in patients with CD20+ aggressive lymphomas into half. In this review the current role of monoclonal antibodies in the treatment of different hematological neoplasms will be discussed and perspectives for their future use in leukemia and lymphomas will be shown.