There is a growing unmet need for more effective treatment of obesity and its complications. While current anti-obesity medications are effective and offer real clinical benefits over diet and lifestyle interventions, they cannot meet the levels of efficacy and reduction of hard endpoint outcomes seen with bariatric surgery. As knowledge on the control of body weight unravels, the complexity of this physiology opens the opportunity to new druggable targets. Currently, gut peptide analogues such as semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, and the dual agonist GLP-1 and gastric inhibitory polypeptide (GIP) tirzepatide are the furthest advanced in clinical development and seem likely to meet current regulatory requirements within the next year or so. However, current regulatory requirements are out of step with the efficacy of new compounds and concepts relating to obesity and its complications. Many other drugs in early development will target different pathways of energy balance, raising the possibility of drug combinations to maximise efficacy as for other chronic disease such as hypertension and diabetes. This will allow more complex and personalised guidelines to evolve.