Sleep has been observed in all vertebrates studied and in several invertebrates, notably the fruit fly Drosophila melanogaster. In all species, a substantial portion of life is spent in this behavioral state and disturbed sleep or lack of sleep has immediate negative impacts on performance and health. Although it is agreed upon that sleep fulfills a fundamental biological need, the function of sleep remains an enigma. Because the expression and regulation of sleep and some sleep disorders have strong genetic components, the recent progress in human, mouse, and fruit-fly genome sequencing projects have given rise to the expectation that the molecular pathways underlying sleep disorders and sleep regulation or even function can now be more readily identified. We review here available genetic data both from basic sleep research and sleep disorders with emphasis on recent advances in our understanding of the molecular basis of the homeostatic regulation of sleep. Recent studies in the dog, the mouse, and the fruit-fly have begun to reveal exciting new molecular pathways that regulate sleep. This illustrates that only the continued use of multiple animal models and genetic approaches will ensure a rapid progress in the relatively new field of sleep genetics.