Caffeine use in the population is widespread. Caffeine withdrawal in the hospital setting is an underappreciated syndrome with symptoms including drowsiness, difficulty concentrating, mood disturbances, low motivation, flu-like symptoms, and headache. Withdrawal may occur upon abstinence from chronic daily exposure at doses as low as 100 mg/day and following only 3-7 days of consumption at higher doses. There are limited data investigating how caffeine withdrawal contributes to hospital morbidity. Some studies suggest caffeine withdrawal may contribute to intensive care delirium and that caffeine may promote wakefulness post-anesthesia. Caffeine supplementation has also shown promise in patients at risk of caffeine withdrawal, such as those placed on nil per os (NPO) status, in preventing caffeine withdrawal headache. These data on caffeine supplementation are not entirely consistent, and routine caffeine administration has not been implemented into clinical practice for patients at risk of withdrawal. Notably, caffeine serves a therapeutic role in the hospital for other conditions. Our review demonstrates that caffeine is largely safe in the general population and may be an appropriate therapeutic option for future studies, if administered properly. There is a need for a randomized controlled trial investigating in-hospital caffeine supplementation and the population that this would best serve.