In the last decade, cross-sectional and multiple cohort studies have associated total fluid intake or water intake with the risk for chronic kidney disease (CKD) and even the risk of developing hyperglycemia. Urine biomarkers have also been linked to the risk of CKD and lithiasis, and these biomarkers respond quickly to variations in fluid intake. High circulating copeptin levels, a surrogate marker of arginine vasopressin, have been associated with metabolic syndrome, renal dysfunction and increased risk for diabetes mellitus, cardiovascular disease and death. The aim of this paper was to explore how the various findings on water intake, hydration and health are interconnected, to highlight current gaps in our understanding and to propose a model that links water intake, homeostatic mechanisms to maintain water balance and health outcomes. Since plasma copeptin and vasopressin have been demonstrated to be sensitive to changes in water intake, inversely associated with 24-hour urine volume, and associated with urine biomarkers and fluid intake, vasopressin is proposed as the central player in this theoretical physiological model.