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This chapter reviews the use of genetics in Drosophila to advance sleep research. Short-term memory can be evaluated in flies using an associative learning paradigm, aversive phototaxic suppression (APS). In 2008, the ventral lateral neurons (LNvs) were shown to promote wakefulness [44-46]. The LNvs are an extensively well-studied neuronal group that is a key part of the clock neurons network that controls circadian behaviors such as locomotor activity rhythms. Plasticity and memory consolidation only represent one of potential avenues for pursuing sleep function, many of the studies that have used Drosophila genetics to pursue functional questions focused on the relationship between sleep and plasticity. Along with the growing genetic toolbox it seems that the fly, in combination with human genetic studies, is uniquely poised to push our understanding of sleep mechanisms and function rapidly forward.