Our review of the literature demonstrates that the search for epigenetic biomarkers for substance use disorders is progressing and in certain cases, shows considerable promise. The search for smoking biomarkers is the most advanced, with multiple sites showing replication and potential for translation to clinically validated biomarkers. The literature for alcohol is much more limited with a few more recent studies using Illumina’s methylation array platforms finding potential loci reflecting alcohol use patterns, albeit with more subtle signals as compared to smoking. Finally, for other substances such as cannabis, opioids, and psychostimulants, the evidence is still more limited, with either a few candidate gene studies (opioids, cannabis), or in the case of psychostimulants, no studies using peripherally available tissue from living human subjects. Clearly, the way forward is to conduct larger studies with careful phenotyping, using a variety of study designs and a variety of populations in order to capture more robust signals. Of note, supplemental network and pathway analyses may be useful even in the absence of highly significant findings in order to elucidate the underlying biology of chronic