Physical activity (PA) and diet directly influence obesity and metabolic syndrome (MS) as important determinants of body composition. Understanding how PA relates to MS in youth is of great importance, and could offer a common strategy for clinical and public health approaches to control this condition. The underlying disorder of MS is a condition of insulin resistance, and a strong relationship between PA level and insulin sensitivity is clearly ascertained. The type, duration, frequency and intensity of PA affect fuel metabolism, in particular carbohydrate and lipid oxidation. The possible modulation of metabolism because of increased fat oxidation by PA is the basis for both prevention and restoration of insulin resistance and MS in obese children. In daily clinical practice, diet followed by pharmacologic treatment are usually the approaches taken, whereas PA is often considered just a suggestion. Although diet and PA have different effects on body composition, with both contributing to fat loss, only PA increases muscle mass and thus has a direct effect on metabolic function, expressed by changes in cardiovascular risk factors. Therefore, it is important to remember their complementary but different targets in daily clinical practice, such as body weight control for diet and metabolic health for PA. In this review, we have summarized the literature on the relationship between PA and MS in pediatrics. Then, we have analyzed the possibility of using PA for MS treatment, as an alternative to drugs, by discussing the results of intervention studies, reasons for low compliance to PA, related benefits, adherence difficulties and costs. Finally, we have tried to suggest recommendations for a multiple-step PA strategy in children and adolescents at risk for MS, by considering PA as the 'key' player in treatment.