Obesity is a complex endocrine disease, mainly caused by environmental, behavioral and biological factors. Maintaining weight loss is extremely difficult due to the neuro-endocrine dysregulations that stimulate the body to return to the previous, increased, weight. Identifying underlying weight-gaining factors is needed, including medication-related, psychological and endocrine factors, as well as monogenic obesity. The cornerstone of treatment is optimization of lifestyle and all other contributing factors. Achieving at least 5% weight loss already has important health benefits. If combined lifestyle intervention (CLI) alone is not successful, pharmacotherapy or bariatric surgery can be added for patients with increased weight-related health risks. Recently, novel pharmacotherapy became available, among which, liraglutide 3 mg and the combination therapy naltrexone/bupropion, which leads to an additional 5-6% mean weight loss compared to CLI alone. For rare forms of obesity there are specific drugs that target defects in the regulation of hunger and satiety. Promising new pharmacotherapy for obesity is under development.