Abstract: Although traditional chemotherapy and hematopoietic stem cell transplantation have each achieved beneficial effects in treating acute myeloid leukemia (AML), effects on long-term prognosis are still limited. To improve upon their deficits, antibody–drug conjugates (ADCs) may be the best choice for patients with AML. Gemtuzumab ozogamicin (GO) is an ADC composed of a humanized anti-CD33 monoclonal antibody linked to the DNA intercalator calicheamicin (CLM). CD33 is an antigen expressed on the surface of more than 90% of AML cells, but not on normal hematopoietic stem cells or mature granulocytes, making it a promising specific target for targeted AML therapy. Many studies have shown that GO monotherapy or combination therapy can improve prognosis for patients with CD33 positive AML. In this review, progress in researches aimed at mechanistically understanding GO therapy in patients with CD33 positive AML is briefly summarized.