The objective of the present systematic review was to investigate whether physical fitness in childhood and adolescence is a predictor for cardiovascular disease risk factors, events and syndromes, quality of life and low back pain later in life. Physical fitness-related components were: cardiorespiratory fitness, musculoskeletal fitness, motor fitness and body composition. Adiposity was considered as both exposure and outcome. The results of 42 studies reporting the predictive validity of health-related physical fitness for cardiovascular disease risk factors, events and syndromes as well as the results of 5 studies reporting the predictive validity of physical fitness for low back pain in children and adolescents were summarised. We found strong evidence indicating that: higher levels of cardiorespiratory fitness at childhood and adolescence are associated with healthier cardiovascular profile later in life. Muscular strength improvements from childhood to adolescence are negatively associated with changes in overall adiposity. A healthier body composition at childhood and adolescence is associated with a healthier cardiovascular profile later in life, and with a lower risk of death. The evidence was moderate for the association between changes in cardiorespiratory fitness and cardiovascular disease risk factors, and between cardiorespiratory fitness and the risk of developing metabolic syndrome and arterial stiffness. We also found moderate evidence on the lack of relationship between body composition and low back pain. Due to a limited number of studies, we found inconclusive evidence for a relationship between muscular strength or motor fitness and cardiovascular disease risk factors, and between flexibility and low back pain.