Animals inhabiting xeric environments use a variety of behavioral and physiological strategies to balance water budgets. We studied the potential contribution of the urinary bladder to osmoregulation in a large desert lizard, the Gila monster Heloderma suspectum. Here we present results of a series of in vivo laboratory experiments which tested the hypothesis that the Gila monster urinary bladder serves as a physiological reservoir, as in amphibians and chelonians, providing water that buffers increases in plasma osmolality when food and water are unavailable. Adult Gila monsters absorbed water from the urinary bladder into circulation and absorption of water from the urinary bladder and drinking water provided similar osmoregulatory benefits within 24 h, although drinking water provided a more immediate osmotic benefit. During food and water deprivation, plasma osmolality increased 2.5 times faster in lizards with an empty urinary bladder compared with those with a full bladder. During rehydration, stereotyped binge drinking behavior increased body mass nearly 22%, which resulted in a 24% reduction in plasma osmolality and a substantial increase in bladder water within 24 h. These results support our hypothesis and demonstrate for the first time in an adult lizard that the urinary bladder can function as a long-term physiological water reservoir. This trait can provide a critical benefit to osmoregulation during the 2- to 3-month summer dry season characteristic of the deserts that Gila monsters inhabit.