The elimination of minimal residual disease remains one of the most promising applications of monoclonal antibody (mAb)-based therapies. An early study showed that treatment with iodine-131 (131I)-labeled anti-CD33 mAb M195 had antileukemic effects when given as postremission therapy to patients with acute promyelocytic leukemia (APL) in second remission. This treatment, however, was limited by significant myelosuppression and by the development of neutralizing human antimouse antibodies. Treatment with native HuM195, a humanized version of murine M195, eliminated minimal residual disease detectable by reverse transcription-polymerase chain reaction (RT-PCR) in 50% of patients. Patients with newly diagnosed APL treated with all-trans retinoic acid followed by HuM195 and consolidation chemotherapy had an 87% 3-year disease-free survival. Radioimmunotherapy with short-ranged, high-energy alpha particle-emitting isotopes may increase the potency of native mAbs while avoiding the nonspecific cytotoxicity of beta-emitting constructs. Targeted alpha particle therapy with bismuth-213-HuM195 showed significant antileukemic activity in patients with relapsed or refractory acute myelogenous leukemia. Antibody-drug conjugates, such as gemtuzumab ozogamicin, composed of a humanized anti-CD33 mAb and calicheamicin, have produced complete remissions in patients with relapsed AML and are likely to be active in the postremission setting.