Emerging evidence suggests a long-term health benefit induced by exercise, persisting beyond exercise cessation. For example, in childhood and adolescence, regular physical activity establishes foundational metabolic and epigenetic programming, reducing risks of obesity, hypertension, type 2 diabetes, and cardiovascular morbidity in adulthood. Exercise in adults also enhances cardiovascular health, metabolic homeostasis, and neurocognitive resilience, delaying age-related cognitive decline and neurodegenerative disorders in aging. These advances indicate an enduring potential of exercise to positively impact health over time. At the molecular level, exercise induces extensive epigenetic modifications (DNA methylation, histone modification, and noncoding RNAs), metabolic reprogramming, and skeletal muscle adaptations (“muscle memory”), which collectively underpin its long-term biological effects. This chapter discusses the evidence on the long-term health benefits of exercise across the lifespan, and advocates for public health policies promoting physical activity across all life stages to combat diseases and support healthy aging.