Interferon (IFN) has diverse acitvities against the proliferation and function of various tumor cells. Recently, IFN-α has been widely used in the treatment of several hematological malignancies including chronic myelogenous leukemia (CML), multiple myeloma, and hairy cell leukemia. IFN-α is becoming a first-choice drug in the treatment of CML, because it has been reported to suppress or abolish the Ph1 chromosome in CML patients. IFN-α is used in combination with conventional chemotherapeutic regimens in the treatment of multiple myeloma. There are many ongoing trials that include IFN-α in their regimens to determine whether or not the prognosis of multiple myeloma can be improved. Although the precise mechanism of the action of IFN has not been fully explained, the clinical applications of IFN for various hematological malignancies are expanding.