Sleep has been identified in all mammals and nonmammalian vertebrates that have been critically evaluated. In addition, sleep-like states have also been identified and described in several invertebrates. Despite this prevalence throughout the animal kingdom, the function of sleep remains a mystery. The completion of several genome sequencing projects has led to the expectation that fundamental aspects of sleep can be elucidated through genetic dissection. Indeed, studies in both the mouse and fly have begun to reveal tantalizing suggestions about the underlying principles that regulate sleep homeostasis. In this article we will review recent studies that have used genetic techniques to evaluate sleep in the fruit fly and the mouse.