Sleep is a fundamental behavior in higher animals that has been firmly established to be under substantial genetic control. However, the identification of individual genes responsible for primary sleep-wake traits has largely eluded researchers. Genetic studies in animal models have uncovered a variety of genomic loci associated with specific traits, validated the role of key neurotransmitter systems (i.e., monoamines) in sleep-wake regulation, identified novel and unexpected genes responsible for controlling sleep-wake traits, and demonstrated substantial genetic overlap in the regulation of sleep and circadian rhythms. Future studies are expected to reveal additional genes and gene networks underlying certain sleep-wake traits, thereby advancing our understanding of the molecular basis of sleep, which may suggest answers to the ultimate question of why we sleep as well as provide unique insight into the relationship between sleep and chronic diseases.