Breast cancer remains a leading cause of cancer-related mortality worldwide, with elderly patients (aged >
65 years) comprising a substantial portion of those affected. The treatment of breast cancer in this population is often complicated by frailty, comorbidities and polypharmacy. This review explores the application of antibody-drug conjugates (ADCs), such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), in treating breast cancer among elderly populations. The underrepresentation of older patients in clinical trials complicates efficacy and safety assessments in this group. Current evidence indicates that ADCs are both effective and tolerable in elderly patients, demonstrating improved progression-free survival (PFS) and overall survival (OS) alongside a manageable safety profile. Data from several trials like the EMILIA, TH3RESA and DestinyBreast studies demonstrate that T-DM1 and T-DXd maintained benefit in PFS and OS for HER2-positive breast cancer in older patients, despite a slight increase in adverse events. The ASCENT and TROPiCS-02 trials further confirm that SG provides significant improvements in PFS and OS in elderly patients at the cost of an increase in some toxicity. Emerging ADCs, including datopotamab deruxtecan and ARX-788, show promise but lack extensive geriatric-specific data. While the ADCs offer encouraging results in terms of efficacy and safety, with appropriate dose adjustments, further research is needed to optimize their use in elderly patients with breast cancer.