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Obesity is a chronic condition associated with risk factors for many medical complications and comorbidities such as cardiovascular diseases, some types of cancer, osteoarthritis, hypertension, dyslipidemia, hypercholesterolemia, type-2 diabetes, obstructive sleep apnea syndrome, and different psychosocial issues and psychopathological disorders. Obesity is a highly complex, multifactorial disease: genetic, biological, psychological, behavioral, familial, social, cultural, and environmental factors can influence in different ways. Evidence-based strategies to improve weight loss, maintain a healthy weight, and reduce related comorbidities typically integrate different interventions: dietetic, nutritional, physical, behavioral, psychological, and if necessary, pharmacological and surgical ones. Such treatments are implemented in a multidisciplinary context with a clinical team composed of endocrinologists, nutritionists, dietitians, physiotherapists, psychiatrists, psychologists, and sometimes surgeons. Cognitive behavioral therapy (CBT) is traditionally recognized as the best established treatment for binge eating disorder and the most preferred intervention for obesity, and could be considered as the first-line treatment among psychological approaches, especially in a long-term perspective; however, it does not necessarily produce a successful weight loss. Traditional CBT for weight loss and other protocols, such as enhanced CBT, enhanced focused CBT, behavioral weight loss treatment, therapeutic education, acceptance and commitment therapy, and sequential binge, are discussed in this review. The issue of long-term weight management of obesity, the real challenge in outpatient settings and in lifestyle modification, is discussed taking into account the possible contribution of mHealth and the stepped-care approach in health care.