Intradialytic hypotension likely results from hypovolemia as well as patient and dialysis-specific factors. An impaired vasoconstrictive response to volume loss during hemodialysis has been demonstrated and increasing evidence suggests that deficiency in the hormone arginine vasopressin may be a contributing factor. Although vasopressin is widely recognized for its role in the regulation of serum osmolality, vasopressin is also an important regulator of blood pressure in health and in various disease states. That vasopressin deficiency contributes to the pathogenesis of intradialytic hypotension is suggested by several observations. First, vasopressin levels typically fall during hemodialysis when a rise might be expected as a result of volume loss. Second, therapies that prevent a fall in osmolality during dialysis, including dialysis against a high sodium bath and isolated ultrafiltration, have been shown to improve intradialytic blood pressure stability. Finally, and perhaps most importantly, the administration of low-dose exogenous vasopressin during dialysis has been shown to support blood pressure and improve volume removal. Further research is needed to determine the effect of chronic vasopressin (or selective V1a agonist) administration during dialysis on volume removal, inter- and intradialytic blood pressure control, and, ultimately, clinical outcomes in end-stage renal disease patients on dialysis.