Obesity represents a major health problem worldwide and is associated with increased prevalence of numerous health-related conditions, including diabetes, hypertension, cardiovascular disease, some forms of cancer and musculoskeletal disorders, among others. Studies that have examined the impact of physical exercise combined with energy restriction diets on weight have shown greater weight loss compared to interventions of exercise-only. Accordingly, the most effective approach to achieve significant weight loss includes a combination of diet, exercise and behavioral strategies. Current guidelines recommend participating in at least 150 minutes of moderate-intensity or 75 minutes of vigorous intensity aerobic exercise weekly, and resistance/muscle strengthening training, involving all major muscle groups at least twice a week. For patients seeking to maintain weight loss, high levels of exercise (225-420 min/week of moderate intensity exercise) have been associated with improved weight maintenance compared to lower levels (<150 min/week). Weight loss has been associated with improvements in prevalence and severity of several obesity associated comorbidities such as insulin resistance, inflammation, dyslipidemia, hypertension, metabolic syndrome, diabetes, pulmonary disease and cardiovascular disease. This review summarized the current knowledge regarding the role of exercise in prevention of weight gain, weight loss and maintenance of weight loss in obese individuals, also outlining the data on effects of exercise on complications of obesity and highlighting areas for future research.