Obesity and overweight are actual chronic conditions 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, OSAS, different psychosocial issues and psychopathological disorders. Obesity is a highly complex, multifactiorial disease: genetic, biological, psychological, behavioral, familiar, social, cultural and environmental factors can influence in different ways. Evidence-based interventions 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, dieticians, physiotherapists, psychiatrists, psychologists, and sometimes surgeons. Cognitive Behavioral Therapy (CBT) is traditionally recognized as the best established treatment for binge-eating disorder (BED) and the most preferred intervention in obesity and could be considered as the first-line treatment among psychological approaches, but does not necessary produce a successful weight loss, above all in a long-term perspective. Traditional CBT for weight loss and other protocols, such as CBT-E, CBT-Ef, Behavioral Weight Loss Treatment (BWLT), Therapeutic Education, Acceptance and Commitment Therapy (ACT), Sequential Binge (SB), are discussed. 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.