After a long and challenging history, there have finally been major breakthroughs in the development of effective obesity medications. Agents that act at receptors of one or more gut hormones are achieving unprecedented weight reductions and improvements in cardiovascular risk factors, comparable to some bariatric surgical procedures. Importantly, there is evidence of beneficial effects on a growing range of conditions, including type 2 diabetes, fatty liver, chronic kidney disease, obstructive sleep apnea and cardiovascular disease. Barriers to access need to be overcome to allow the standard of care for obesity to match that of other chronic diseases.