This narrative review evaluates the current literature to provide insights into the role of physical inactivity in the development of chronic diseases and premature death. The review confirms that regular physical activity is effective in preventing several chronic diseases, including cardiovascular disease, diabetes, cancer, hypertension, obesity, depression, and osteoporosis, and reduces the risk of premature death. The Health Canada physical activity guidelines are deemed sufficient to elicit health benefits, especially in previously sedentary individuals. There is a linear relationship between physical activity and health status, with further increases in physical activity leading to additional improvements in health. Physical inactivity is a modifiable risk factor for various chronic diseases, and its prevalence among adults is higher than that of other modifiable risk factors. The review also discusses the evidence for physical fitness and musculoskeletal fitness, and the independent effects of frequency and intensity of physical activity. The benefits of physical activity are evident in both primary and secondary prevention, with significant reductions in all-cause and cardiovascular-related mortality. Regular physical activity is particularly beneficial for preventing type 2 diabetes, cancer, and osteoporosis. The review highlights the importance of engaging in physical activity to maintain health and reduce the risk of chronic diseases.This narrative review evaluates the current literature to provide insights into the role of physical inactivity in the development of chronic diseases and premature death. The review confirms that regular physical activity is effective in preventing several chronic diseases, including cardiovascular disease, diabetes, cancer, hypertension, obesity, depression, and osteoporosis, and reduces the risk of premature death. The Health Canada physical activity guidelines are deemed sufficient to elicit health benefits, especially in previously sedentary individuals. There is a linear relationship between physical activity and health status, with further increases in physical activity leading to additional improvements in health. Physical inactivity is a modifiable risk factor for various chronic diseases, and its prevalence among adults is higher than that of other modifiable risk factors. The review also discusses the evidence for physical fitness and musculoskeletal fitness, and the independent effects of frequency and intensity of physical activity. The benefits of physical activity are evident in both primary and secondary prevention, with significant reductions in all-cause and cardiovascular-related mortality. Regular physical activity is particularly beneficial for preventing type 2 diabetes, cancer, and osteoporosis. The review highlights the importance of engaging in physical activity to maintain health and reduce the risk of chronic diseases.