Neurobehavioral responses to acute total and chronic partial sleep deprivation occur in healthy adults and are particularly evident in vigilant attention performance. There are large inter-individual differences in the degree of cognitive deficits--such differences are manifested in proportionality between the mean and variance as sleep loss progresses. It has recently been demonstrated via laboratory experiments that differential neurobehavioral vulnerability to sleep deprivation is not random--but rather is stable and trait-like--strongly suggesting a phenotypic response with possible genotypic involvement. These experiments also showed that vulnerability was not explained by subjects' baseline functioning or a number of other potential predictors. Differential vulnerability has been shown to extend to chronic partial sleep deprivation. One potential genetic biomarker for such differential vulnerability is the human leukocyte antigen (HLA) DQB1*0602, an allele which we recently demonstrated predicts interindividual differences in sleepiness, physiological sleep, and fatigue to chronic partial sleep deprivation in healthy adults. Determination of biomarkers of individual differences to sleep loss will help identify those individuals in the general population who are most in need of prevention of sleep debt and in need of effective countermeasures for sleep loss; will further understanding and management of vulnerability to excessive sleepiness due to common sleep and medical disorders; and will inform public policies pertaining to the need for adequate sleep.