The high remission rates observed in patients with chronic myelogenous leukemia who receive Imatinib mesylate (Gleevec) indicate that targeted therapy for hematological malignancies is achievable. At the same time, progress in cellular biology over the past decade has resulted in a better understanding of the process of malignant transformation, a better classification of subtypes of each disease on the basis of molecular markers, and a better characterization of the molecular targets for drug development. These advances have already spawned the development of such effective agents as monoclonal antibodies and specific enzyme inhibitors. This review attempts to provide a practical introduction to the complex and growing field of targeted therapy in hematological malignancies.