Circadian (~24 hour) clocks are endogenous mechanisms that time the recurring, daily activities observed in most organisms. These clocks are genetically regulated, and generate biochemical oscillations within individual cells composing most tissues. Our work began in Drosophila melanogaster, where we identified a small group of genes that are principal components of an intracellular circadian clock. Mutations in any of these genes can lengthen or shorten the period of behavioral and other circadian rhythms or can abolish the rhythms altogether. The abundance of proteins encoded by several of these genes changes rhythmically with a circadian period. Mutations affecting any of these genes have corresponding effects on behavioral rhythms as well as the molecular rhythms of hundreds of clock-regulated genes that are expressed in most organ systems. Orthologous genes regulate mammalian, including human, circadian rhythms, so that today our lab studies the action of these genes and proteins in a variety of biological models. We are also currently studying prominent rhythmic behaviors that are controlled by circadian clock with a particular focus on sleep. Recently our laboratory has searched for and identified genes that affect the homeostatic regulation of sleep in Drosophila. This research has uncovered specific neurons whose activity promotes sleep.