Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), particularly in the relapsed or refractory settings, traditionally associate with poor prognoses following treatment with cytotoxic chemotherapeutic agents. Advances in treatment options that utilize immunotherapy have strongly impacted the treatment landscape for patients with these diseases. The oldest form of immunotherapy is allogeneic hematopoietic stem cell transplantation which harnesses the power of the donor immune system to prevent relapse of the recipient’s leukemic clone. There are currently multiple immunotherapies approved for the treatment of ALL including the monoclonal antibody rituximab, the bispecific T-cell engager blinatumomab, the antibody-drug conjugate inotuzumab ozogamicin, and the chimeric antigen receptor T-cell products tisagenlecleucel and brexucabtagene autoleucel. The antibody-drug conjugate gemtuzumab ozogamicin is currently approved for treatment of AML, and the cytokine-based therapy tagraxofusp is approved for treatment of blastic plasmacytoid dendritic cell neoplasm, a rare type of acute leukemia. There are several other immunotherapies that are currently under investigation including monoclonal antibodies, bispecific antibodies, chimeric antigen receptor T-cell products, natural killer cell products, vaccine therapies, and immune checkpoint inhibitors. This chapter will provide an overview of the development of these immunotherapies for the treatment of adults with ALL or AML.