The field of sleep research has seen massive advances in the last decade, from basic findings in genetics and neurophysiology to understanding and quantifying the effects of fatigue. Furthermore, mathematical models have been widely successful, not only in predicting experimental results, but also in improving (and sometimes redefining) our understanding of the underlying physiological mechanisms. Translating our current wealth of knowledge into real-world applications will require interactions among experimentalists, modelers, and policymakers. In this seminar, we will promote a mutually beneficial dialogue between leading modelers and experimentalists in tackling the current theoretical challenges in sleep and circadian modeling. We will also explore the potential uses of mathematical models in real-world environments, such as identifying and quantifying the risks associated with drowsy driving, and discuss how drowsy driving can and should be managed within legal, ethical, and societal frameworks. Drowsiness (or sleepiness) surpasses alcohol and drugs as the greatest identifiable and preventable cause of accidents in all modes of transport. We have assembled a multidisciplinary group of participants—spanning sleep medicine, law, policy, occupational health, transportation, and law enforcement—to explore innovative solutions.