Senescent cells accumulate throughout tissues as we age, releasing inflammatory factors through their senescence-associated secretory phenotype (SASP) that impair tissue repair and regeneration. Senolytic drugs specifically target these dysfunctional cells for elimination, while exercise training also demonstrates senolytic effects, creating a potential dual intervention strategy for cardiac and skeletal muscle rejuvenation. This convergence of pharmacological and lifestyle interventions represents a sophisticated approach to combating one of aging's fundamental mechanisms. The SASP response creates a cascade of tissue dysfunction that extends far beyond the senescent cells themselves, making their elimination particularly attractive for therapeutic intervention. While senolytics like dasatinib plus quercetin have shown promise in early human trials, the addition of exercise's natural senolytic properties could amplify benefits while providing complementary muscle-strengthening effects. However, the field remains in its infancy regarding optimal dosing protocols, timing of interventions, and long-term safety profiles. The challenge lies in translating promising preclinical results into practical clinical applications, particularly determining whether combination approaches offer synergistic benefits over individual interventions for healthy aging populations.