Regular physical activity (PA) is both a preventive measure and a cure for non-communicable diseases. Moreover, PA improves mental health, quality of life, and well-being. Conversely, physical inactivity and sedentary lifestyles have negative impacts on individuals, families, and society, as evidenced in particular by the spread of the obesity epidemic. PA has proven to be a low-cost alternative for the treatment and prevention of disease. Therefore, interventions to prevent avoidable diseases by increasing the proportion of physically active people are fundamental. The Special Issue "Physical Activity, Wellness and Health: Challenges, Benefits and Strategies" was collected research articles on anthropometric determinants of health and performance, PA and healthy habits, exercise and diet, exercise and body composition, interventions to promote PA for people of all ages, strategies for the implementation of an active life, and the beneficial effects of exercise on metabolic syndrome. A total of 20 articles were published, falling mainly into the following three areas: anthropometry, health, and sport; health benefits of exercise; population studies and strategies for an active life. All of the studies support strategies to promote PA and reduce sedentary behavior among adolescents, adults and the elderly. There is no doubt that regular exercise is beneficial to health, but the general population should be encouraged to engage in more of it.