Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO₂max), is related to functional capacity and human performance and has been shown to be a strong and independent predictor of all-cause and disease-specific mortality. The purpose of this review is to emphasize age-related physiological adaptations occurring with regular exercise training, with specific reference to the main organs (lung, heart, skeletal muscles) involved in oxygen delivery and utilization as well as the importance of exercise training for promoting life expectancy in clinically referred populations. As yet, it is not possible to extend the genetically fixed lifespan with regular exercise training, but to give the years more life. This is where physical fitness plays an important role.