Mylotarg® (gemtuzumab ozogamicin) was the first antibody-drug conjugate approved for treatment of acute myeloid leukemia (AML) by the Food and Drug Administration via the accelerated approval process in 2000. Mylotarg® consists of an antibody directed toward the CD33 antigen conjugated to the antitumor antibiotic, calicheamicin. Mainly due to concerns about the safety profile and lack of improvement of clinical benefit in post-approval clinical trials, the drug was voluntarily withdrawn from the market by Wyeth in October 2010. Following its withdrawal from the market, results from several clinical trials warranted revisiting the clinical use of the drug when used at a low-dose range in newly diagnosed AML with favorable cytogenetics. The significant clinical evidence led to the eventual reapproval of Mylotarg® in 2017, following a new dosing regimen and lower recommended dose.