Blood cancers in general include leukemia, lymphoma, and multiple myeloma. Collectively, these cancers are the fifth most commonly occurring cancers and the second leading cause of cancer death. These disorders are characterized by the accumulation of malignant cells, resulting in aggressive clinical manifestations. The therapeutic approach to these disorders is basically chemotherapy based on the concept of total cell kill. However, severe side effects and complications such as serious infection and bleeding due to anti-cancer drugs are major problems in the clinical settings. These problems occur because anti-cancer agents have effects on both normal and malignant hematopoietic cells. Targeted therapies attack the physiological pathway of hematopoiesis and so can be used as therapy if tumorgenesis happened. They display a variety of drugs either approved by FDA for use or still in clinical trials. These targeted therapies include tyrosine kinase inhibitors especially Gleevec. Tumor vaccines is a promising option for cellular mediated immunity against cancer in affected patients. Monoclonal antibodies, the widely used model of targeted therapy in hematological malignancies especially in lymphoma. Rituximab (anti CD20) is discussed in details regarding benefits and side effects. Proteasome inhibitors such as valcade; the promising treatment in MM. Finally, angiogenesis inhibitors is a recent modality of treatment targeting angiogenesis process which is vital for tumor growth. 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.