All animals studied to date exhibit sleep or sleeplike behavior, but sleeping animals are at risk because they are generally unaware of and unresponsive to the environment. Selection should favor animals that make good trade-offs between sleep attributes (e.g., location, timing, duration) and predation risk; in other words, sleep should be facultative. The few studies that document sleep plasticity in response to predation risk have focused on endothermic vertebrates. We tested the hypothesis that a representative ectothermic vertebrate, the Desert Iguana (Dipsosaurus dorsalis), exhibits behavioral sleep plasticity in response to predation risk. We found a reduction (>50%) in total sleep time during daylight when Desert Iguanas were exposed continuously to a Sidewinder (Crotalus cerastes) in a laboratory setting. During asynchronous eye closure (ASEC) bouts, the eye of the iguana distant to the Sidewinder was more often closed, whereas the proximal eye was more often open, suggesting unihemispheric sleep (which has not been confirmed yet in reptiles) to maintain vigilance. Desert Iguanas spent more time aboveground and less time within their burrows when the Sidewinder was present. Snake activity was minimal, with movements occurring just 1.1% of the time, suggesting that iguanas were not merely responding to a moving object. Our findings suggest that Desert Iguanas will forgo sleep and remain vigilant when the potential for predation is increased. These findings illustrate the importance of ecology in shaping the behavior and probably the associated physiological and neurological attributes of sleep in ectothermic vertebrates.