Abstract: Antibody–drug conjugates (ADCs) represent a new class of antitumor agents composed of an antibody, a cytotoxic drug, and a flexible linker, which together provide highly tumor-specific targeting and potent antitumor activity. For patients with human epidermal growth factor receptor-2 (HER-2)-positive advanced breast cancer who have failed to respond to previous multiline therapies, the next-generation ADC, DS-8201a, delivers a good therapeutic effect as measured by disease control rate and improved survival. It also provides a survival benefit to patients with advanced breast cancer with low HER-2 expression. Drug-related hematological toxicity, interstitial pulmonary disease, and other safety issues have also attracted widespread attention. Here, we reviews the researches addressing the efficacy and safety of DS-8201a in the treatment of advanced breast cancer.