The objective of the present systematic review was to investigate whether physical fitness in childhood and adolescence is a predictor of cardiovascular disease (CVD) 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 CVD risk factors, events and syndromes as well as the results of five studies reporting the predictive validity of physical fitness for low back pain in children and adolescents were summarised. Strong evidence was found indicating that higher levels of cardiorespiratory fitness in childhood and adolescence are associated with a 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 in 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 CVD risk factors, and between cardiorespiratory fitness and the risk of developing the metabolic syndrome and arterial stiffness. Moderate evidence on the lack of a relationship between body composition and low back pain was found. Due to a limited number of studies, inconclusive evidence emerged for a relationship between muscular strength or motor fitness and CVD risk factors, and between flexibility and low back pain.