Sensitivity to ethanol intoxication, propensity to drink ethanol and vulnerability to develop alcoholism are all influenced by genetic factors. Conversely, exposure to ethanol or subsequent withdrawal produce gene expression changes, which, in combination with environmental variables, may participate in the emergence of compulsive drinking and relapse. The present review offers an integrated perspective on brain gene expression profiling in rodent models of predisposition to differential ethanol sensitivity or consumption, in rats and mice subjected to acute or chronic ethanol exposure, as well as in human alcoholics. The functional categories over-represented among differentially expressed genes suggest that the transcriptional effects of chronic ethanol consumption contribute to the neuroplasticity and neurotoxicity characteristic of alcoholism. Importantly, ethanol produces distinct transcriptional changes within the different brain regions involved in intoxication, reinforcement and addiction. Special emphasis is put on recent profiling studies that have provided some insights into the molecular mechanisms potentially mediating genome-wide regulation of gene expression by ethanol. In particular, current evidence for a role of transcription factors, chromatin remodeling and microRNAs in coordinating the expression of large sets of genes in animals predisposed to excessive ethanol drinking or exposed to protracted abstinence, as well as in human alcoholics, is presented. Finally, studies that have compared ethanol with other drugs of abuse have highlighted common gene expression patterns that may play a central role in drug addiction. The availability of novel technologies and a focus on mechanistic approaches are shaping the future of ethanol transcriptomics.