Insects are a highly successful class of arthropods consisting of diverse species adapted to live in many environments across the globe. Insects can increase their survivability by avoiding harmful compounds in their environment. Here, we investigate innate avoidance pathways from five species of Drosophila at different evolutionary distances to determine the degree to which different species have adapted to avoid odorants in the environment. In examining D. melanogaster, D. yakuba, D. suzukii, D. pseudoobscura, and D. virilis, we have determined that avoidance to repellents such as carbon dioxide, ethyl-3-hydroxybutyrate, and citronellal vary greatly across these species. For example, D. melanogaster robustly avoids carbon dioxide, while D.suzukii has olfactory neurons that can respond to carbon dioxide but behaviorally does not avoid carbon dioxide. On the other hand, DEET, a synthetic chemical, is observed to be highly repellent across all species tested behaviorally. In this analysis, the role of olfactory neurons in DEET avoidance is investigated. In addition, the relationship between compound vapor pressure and avoidance is tested. Results presented here imply that the chemosensory mechanism these Drosophila species use to avoid DEET is dependent on multiple factors and complex. Nevertheless, we have identified several related chemicals that appear to be highly repellent for D. melanogaster.