Early detection and consequential intervention are key to good treatment outcomes and avoidance of complications for most diseases. Arguably, this may not be the case for Type-2 diabetes (T2D) where measures of elevated glucose and HbA1C, historically related to a predicted onset of retinopathy, occur too late in the pathogenesis of the disease. We require improved markers of T2D are necessary to better diagnose and treat this prevalent disease at early stages. With the advent of precision medicine, now is the time to re-examine the pathogenesis of type 2 diabetes at the molecular level. Which subsets of T2D define the rate of progression to certain diabetes complications? Can early molecular drivers of the disease be better identified? What factors contribute to dysfunctional inter-organ communication and altered metabolic homeostasis? Does pancreatic ß-cell failure really define the disease? If detected early enough, can we envision ways to reverse, or even prevention, of T2D be practically envisioned? With several commonly used T2D therapies soon coming off of patent this may be conceivable. Nonetheless, there remains a need for more effective therapeutic approaches, not just for T2D, but also for its comorbidities. This Keystone Symposium will examine the current knowledge of T2D pathogenesis and the therapeutic landscape - with a view towards earlier diagnosis, more effective and tailored T2D treatment regime(s) that also prevent or significantly delay the journey to complications and comorbidities.