| Summary: | In this review, we discuss reports of genotype-dependent interindividual differences in phenotypic neurobehavioral responses to total sleep deprivation or sleep restriction. We highlight the importance of using the candidate gene approach to further elucidate differential resilience and vulnerability to sleep deprivation in humans, although we acknowledge that other omics techniques and genome-wide association studies can also offer insights into biomarkers of such vulnerability. Specifically, we discuss polymorphisms in adenosinergic genes (<i>ADA</i> and <i>ADORA2A</i>), core circadian clock genes (<i>BHLHE41/DEC2</i> and <i>PER3</i>), genes related to cognitive development and functioning (<i>BDNF</i> and <i>COMT</i>), dopaminergic genes (<i>DRD2</i> and <i>DAT</i>), and immune and clearance genes (<i>AQP4</i>, <i>DQB1*0602</i>, and <i>TNFα</i>) as potential genetic indicators of differential vulnerability to deficits induced by sleep loss. Additionally, we review the efficacy of several countermeasures for the neurobehavioral impairments induced by sleep loss, including banking sleep, recovery sleep, caffeine, and naps. The discovery of reliable, novel genetic markers of differential vulnerability to sleep loss has critical implications for future research involving predictors, countermeasures, and treatments in the field of sleep and circadian science.
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