For translation to clinical applications, several areas are important to consider in the development of epigenetic biomarkers for substance use disorders. First, although substance use disorders are brain-based disorders, brain tissue is not accessible in routine clinical practice. Therefore, this review will focus primarily on findings in tissues that are more easily accessible, such as peripheral leukocytes and saliva samples, with other tissues discussed as relevant to highlight the generalizability of findings. Peripheral tissues do have important limitations with respect to generalizability to other tissues of interest such as the brain [24], but there is increasing evidence that many epigenetic changes found in peripheral leukocytes and transformed lymphoblasts also correspond to changes in brain cells [25].