Adiponectin is a major adipokine that seems to have a crucial role in the protection from many metabolic abnormalities. There have been several reports that suggest a strong inverse relationship between plasma levels of adiponectin and the severity of obesity and its comorbidities, such as insulin resistance, type 2 diabetes and cardiovascular disease. Restoring adiponectin levels has salient benefits in many of the obesity-related diseases, which provides a strong rationale for adiponectin-based therapeutics for treating metabolic abnormalities. A Japanese team of researchers has screened and identified an orally active compound that binds to and activates the adiponectin receptor 1 (AdipoR1) and AdipoR2 receptors that are named AdipRon. This molecule ameliorates insulin resistance and glucose intolerance in obese animal models, and also extends the shortened lifespan of diabetic obese mice. If this work can be extended to humans, the improved safety and efficacy of these orally active adiponectin agonists could offer a promising new approach to treating obesity-related diseases.