To review clinical data regarding the newly approved drug setmelanotide, an injectable melanocortin 4 receptor (MC4R) agonist, for chronic weight management in adults and children aged 6 years and older with monogenic obesity. A literature review was performed by searching MEDLINE, SCOPUS, and EMBASE for all relevant English-language articles published between January 1, 1996, and November 30, 2021, using search terms obesity, setmelanotide, Imcivree, and MC4R agonist. This review included two phase 2, two phase 3, and one ongoing clinical trial evaluating the efficacy and/or safety of setmelanotide. Setmelanotide demonstrates statistically significant weight loss with at least a 10% decrease in body weight after 1 year and decreased appetite in phase 2 and phase 3 clinical trials. The most common adverse effects included injection site reaction (96%), skin hyperpigmentation (78%), nausea (56%), headache (41%), and diarrhea (37%). Setmelanotide is the first and only Food and Drug Administration-approved medication for the treatment of proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, and leptin receptor deficiency in patients with obesity. It may be used in children and adults who have received genetic testing and exhibited extreme obesity before age five. Setmelanotide is a daily subcutaneous injection and may be difficult to afford for patients. Setmelanotide is an effective treatment in patients with obesity and indicated genetic disorders.