Despite recent advances in the treatment of acute myeloid leukemia (AML), relapses remain high, and long-term survival is poor, emphasizing the need for better treatment options. Development of targeted antibody-based immunotherapeutic agents has been an area of growing research in AML. Target antigens of interest include CD33, CD123, CD47, CD70, FLT3, and CLL-1 because of their high expression on AML blasts and leukemic stem cells. Gemtuzumab ozogamicin, a CD33-directed antibody-drug conjugate, is the only Food and Drug Administration-approved monoclonal antibody (mAb) in AML providing evidence for the potential future role of mAb-based therapies in AML. This article provides an overview of the progress made in targeted immunotherapy in AML, particularly focusing on unconjugated and conjugated mAbs.