Transcriptome profiling of postmortem brain tissue from alcoholics and matched controls has revealed novel and detailed gene expression changes, generating new avenues for addiction research. Although there are certain difficulties inherent with using postmortem brain tissue, such as difficulty in obtaining samples and accounting for variable patterns of alcohol use and other human variables, postmortem brain tissue remains the gold standard against which all other model systems should be evaluated. Next-generation sequencing provides a more comprehensive and accurate tool for transcriptome analysis of this limited, valuable resource.