Abstract: Currently, breast cancer is a common malignancy in female, and previous guidelines recommended that one of the key biomarkers for breast cancer, human epidermal growth factor receptor 2 (HER2), is classified as either positive or negative to guide clinicians’ treatment decisions. While nearly half of breast cancer patients have low HER2 expression (IHC expression is 1+ or 2+ and ISH detection is negative), such patients are insensitive to traditional anti-HER2 targeted therapy. However, novel antibody-drug conjugates (ADCs) provide new targeted therapy options for breast cancer patients with low HER2 expression, challenging the traditional binary concept and arousing research enthusiasm. In the latest ASCO/CAP guidelines for HER2 detection in breast cancer, HER2-low breast cancer has been included as a clinical treatment subgroup. This article will review the definition of HER2-low breast cancer, the progress of drug therapy such as ADC, and the current challenges faced by this subgroup.