Lifestyle interventions are the cornerstone of obesity treatment. Patients with genetic obesity often require additional anti-obesity pharmacotherapy to treat their hyperphagia. Treatment aims may differ for genetic obesity as halting the progressive weight gain and ameliorating hyperphagia or quality of life may be considered successful as well. Specific genetic obesity disorders can be effectively treated with targeted anti-obesity medication (AOM), i.e., leptin replacement therapy and MC4R-agonists. Non-targeted AOMs, such as naltrexone-bupropion and glucagon-like peptide-1 analogues, are FDA and EMA approved for obesity as well. Similar efficacy of these agents was observed in small observational studies including patients with genetic obesity, compared to the patients with multifactorial obesity. In the future, new and innovative pharmacotherapeutical options, such as gene therapy, are expected to emerge with positive impacts on body weight, hyperphagia, and, most importantly, the quality of life for patients with genetic obesity disorders.