The pharmacokinetics of a drug are subject to large interindividual variability, which can result in lack of response or adverse drug reactions. In addition to genetic polymorphisms and drug interactions, key genes involved in the metabolism and transport of drugs are demonstrated to have epigenetic influences that can potentially affect interindividual variability in drug response. Emerging studies have focused on the importance of DNA methylation for ADME gene expression and for drug action and resistance, particularly in cancer. However, the epigenetic and ncRNA-dependent regulation of these genes, as well as the pharmacological consequences, is in need of greater attention. In the current review we provide an update of epigenetic and ncRNA-dependent regulation of ADME genes.