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In this review, two issues are highlighted: 1) the difficulties that can form major hurdles in trying to understand a disease or a fundamental biologic process at the genetic and molecular level and 2) the potential opportunities that genetic models such as the Drosophila or c-elegans can provide in answering clinically or biologically relevant questions. This review also lists in some detail the areas in which these models have been helpful and successes have been scored. For such models to be used, however, requires the “dissection” of a biologic or a disease process into a tractable phenotype that can be assayed in a genetic model and have relevant and interpretable conclusions. The hope is that questions pertaining to sleep, arousal, respiratory neurobiology, and their disorders can be formulated in such a way to be addressed in models that can lend themselves to very exciting discoveries.