Alcohol use disorders and alcoholism are prevalent conditions that come at a high cost for individuals and for society at large. About half the factors contributing to the development of these disorders are genetic, yet few of the genes involved are well known or characterized. Invertebrate organisms, especially the vinegar fly Drosophila melanogaster and the roundworm Caenorhabditis elegans, have been successfully used to isolate genes involved in behavioral ethanol responses that are relevant to mammalian alcohol drinking. In addition, because of their genetic accessibility, these invertebrates have been instrumental in deciphering the molecular mechanisms and signaling pathways encompassed by the genes involved in alcohol responses. Here we review the experimental approaches and behavioral paradigms utilized in these organisms and highlight the genetic and molecular insights into the mechanisms of behavioral alcohol responses they have enabled. © 2014 Elsevier Inc. All rights reserved..