by Clayton Baker, Victor A. Ansere, Cossette I. Sanqui, Bérénice A. Benayoun Aging has effects on the immune system that are similar in men and women, but also reshapes their immune systems in unique, sex-specific ways. These sex-specific patterns of immune aging influence disease susceptibility, vaccine effectiveness, cancer survival, and responses to pharmacological therapies, and have direct implications for preventive medicine and clinical care. However, these differences in susceptibilities and responses are rarely considered in research, clinical trials, or treatment guidelines. By integrating knowledge of sex-specific immune aging with real-world outcomes from vaccines, cancer immunotherapy, and pharmacovigilance studies, this Essay argues that accounting for both sex and age is essential to advance personalized medicine.