Background: Type 2 diabetes and its cardiovascular disease complications are the major public health threats of our century. Although physical activity and dietary changes are the cornerstones in prevention of diabetes, their broad implementation is not elementary and other complementary lifestyle regimens are needed. Summary: Vasopressin (VP) is the main regulator of body water homeostasis, and at insufficient water intake, normal plasma osmolality can be maintained by increased pituitary VP secretion through VP-2 receptor mediated renal water reabsorption. During the last 6 years several independent studies have shown that high circulating VP, measured by the stable VP marker copeptin, predicts development of type 2 diabetes as well as the metabolic syndrome, cardiovascular disease and premature mortality. Interestingly, VP stimulates adrenocorticotrophic hormone, and as a consequence cortisol secretion, through pituitary VP-1B receptors, which could explain why the 25% of the middle-aged population with high circulating VP have a mild Cushing's syndrome-like phenotype. In rats, high VP results in deterioration of glucose tolerance whereas low VP, obtained by high water intake, ameliorates the VP associated dysmetabolic state, suggesting that the relationship between high VP and risk of diabetes and cardiometabolic disease in humans may be causal and reversible by increasing water intake. Key Messages: With the emerging evidence that high VP, which is present in 25% of the population, is an independent risk factor for diabetes and cardiometabolic disease, VP reduction through water supplementation appears as an attractive candidate intervention to prevent diabetes and its cardiovascular complications.