Genomic studies often report that a significant fraction of the genome ( up to ~30%) changes expression following exposure to ethanol. Unfortunately, responses important for producing alcohol behaviors can be obscured by this surfeit of changes. Functional alcohol tolerance is alcohol-induced alcohol resistance that is not mediated by a change in alcohol metabolism. To help identify changes important for producing functional behavioral tolerance to alcohol, we exploited the fact that two chemically distinct alcohols produce mutual cross tolerance through a related mechanism. This was demonstrated in detail using the Drosophila slo gene as a test case. In flies, the capacity to acquire tolerance to either ethanol or benzyl alcohol has been linked to the slo gene, which encodes BK-type Ca2+-activated K+ channels. Mutations in slo block the acquisition of tolerance, sedation with either drug induces slo expression, and slo induction has been shown to phenocopy tolerance. A survey of the alcohol-induced changes in histone modification and transcription factor binding across the slo transcriptional control region proved to be an effective way to identify DNA regulatory elements that mediated the alcohol response. Based on the success of this approach, we performed a genomic survey to identify all genes and regions that respond similarly to both benzyl alcohol and ethanol. This technique identified a gene network, shown to play important roles in this alcohol response (tested by mutation, RNAi, or transgenic mis-expression). We also developed profiles for alcohol-induced histone H4 acetylation patterns and CREB-binding patterns across the slo promoter region. These profiles were then used in a ChIP-Seq genomic survey to find other genes with similar patterns. By doing so we have developed a refined profile of one class of alcohol-regulated gene.