Molecular target therapy is progressive and promising in various hematological malignancies. Imatinib is now the treatment of choice for chronic-phase chronic myeloid leukemia. Eight-year data from the pivotal trial of imatinib, the IRIS trial, showed high long-term response rates and favorable tolerability profile compared with previous therapies. For patients with primary resistance to imatinib, hematologic disease recurrence, or emergent BCR-ABL kinase domain mutations, the potent second generation tyrosine kinase inhibitors dasatinib and nilotinib are now available. Since the introduction of all-trans retinoic acid (ATRA) in the 1980s, the strategy for treating acute promyelocytic leukemia (APL) has shifted from conventional chemotherapy to cell differentiation. The combination of ATRA and anthracycline-based chemotherapy is currently the standard approach to treat newly-diagnosed APL. Multiple myeloma (MM) is also one of the major therapeutic targets in using molecular based technology. The recent availability of clinical data regarding thalidomide and lenalidomide has provided effective treatment options for patients with both newly diagnosed and relapsed/refractory MM. Overall, this paper focuses on a comprehensive review of the current literature and provides data supporting molecular target therapy for patients with CML, APL, or MM.