Treatment of hematological cancers has evolved over the years for these deadly blood disorders. The treatment strategy for these disorders has progressed from palliative measures to definitive therapies with curative intent. The treatment outcome of these disorders has also gone from despair to hopefulness, with many of the patients cured of the diseases. Immunotherapy plays a key role in the present management of these disorders. The classical approach was hematopoietic stem cell transplant, which remains as one of the options of treatment with curative intent. However, selection of a suitable donor, procedure-related mortality, and risk of graft versus host disease (GVHD) are some of the challenges faced in this treatment of choice. Near the close of the 1990s, monoclonal antibodies as a form of targeted therapy were approved for blood cancers, such as B-cell malignancies and chronic lymphocytic leukemia (CLL). Since then, more than 100 of these monoclonals with proven safety and efficacy have been introduced, for not only treatment of blood and other cancers but also other diseases as well. Over the years, continual innovations have brought novel immunotherapies for treatment of blood cancers, including the bispecific T-cell engagers, the bispecific NK-cell engagers, the chimeric antigen receptor T-cell/NK-cell (CAR-T/CAR-NK) constructs, and the immune checkpoint inhibitors. These emerging treatment approaches have revolutionized the management of hematological malignancies.