Background: Obesity is a chronic condition with high prevalence and multifaceted aetiology, accompanied by an increased risk of morbidity and mortality. Obesity has several negative effects on the psychological status, and the severity of psychological disorders correlates with the degree of obesity.Objective: Aim of this review is to provide an overview of the literature concerning the psychological distress associated with severe obesity, which contributes to deterioration of the quality of life of affected patients. Methods: Dysfunctional eating behaviours and eating disorders, psychiatric comorbidity, cognition and quality of life will be discussed together with the most common drugs that can be employed to treat the various disorders in this peculiar clinical setting. The effects of bariatric surgery will be also reviewed. Results: Obesity is often the result of pathological behaviours implemented in an eating disorder. Inconsistent results have been reported with regard to the effect of severe obesity on cognition, which recognize a multifaceted aetiology. Serotonergic agents play an important role in the management of patients with obesity and binge episodes, fluoxetine being currently a drug approved for this disorder. The efficacy of lorcaserin, a combination of bupropion and naltrexone, or antiepileptic medications (topiramate and zonisamide) has also been proposed. A neuroprotective role of leptin and oestrogen has been hypothesized. Bariatric surgery is a helpful treatment of morbid obese patients, with long-term favourable results on the psychopathological profile. Conclusion: Psychological, psychoeducational and psychopharmacological treatment can facilitate weight loss in morbid obese subjects with psychopathological comorbidities. A precise definition of the mechanisms affecting appetite, satiety and energy balance is expected to foster the development of new effective antiobesity drugs.