Sleep appears to serve important functions, but why we sleep and how sleep is regulated are not well understood. It is clear, however, that sleep is under circadian control. Our overall goal is to elucidate the molecular and cellular basis of sleep and circadian rhythms. Due to ease of genetic manipulation and molecular analysis, the fruit fly, Drosophila melanogaster, has emerged as a powerful model system for studying sleep and circadian rhythms. Our research strategy is to find Drosophila mutants with a strong and interesting sleep or circadian phenotype and identify the genetic, molecular, and cellular basis for the phenotype. Using this strategy, we have discovered several novel genes [e.g., jetlag (Koh et al, Science, 2006) and sleepless (Koh et al, Science, 2008; Wu et al, Nature Neuroscience, 2010)] and mutations affecting sleep and circadian rhythms. We also employ various genetic tools for targeted gene expression to define novel sleep circuits.