25 years of Drosophila “Sleep genes”

The field of Drosophila sleep research, which began 25 years ago, has identified more than 200 genes influencing sleep. In this review, I summarize the foundation of the field and the growing list of genes implicated in sleep regulation. I compare the genetic methods used to identify genes governing sleep and circadian rhythms and the distinct outcomes of screens for genes regulating these two highly related processes. Finally, I discuss the ~ 200 sleep-regulating genes of Drosophila in the context of recent developments in the field and voice reasons for scepticism regarding the relevance of these genes to the homoeostatic regulation of sleep. Finally, I speculate on the future promise of the fly model system for revealing conserved molecular mechanisms of sleep homoeostasis.