A wide variety of chemical and physical agents have the potential to produce adverse effects by causing heritable changes to the genome, resulting in heritable alterations in phenotype. These are often assumed to be a consequence of mutation. However, mutagenesis is not the only mechanism underlying heritable alterations to the genome. It is important to understand that there may also be an epigenetic basis for this. DNA methylation is the epigenetic mechanism that this review focuses upon. We indicate how altered methylation may play a key role in a variety of chemical-induced toxicities, including, but not limited to, carcinogenesis, and we point out how an assessment of methylation status can provide important information as a component of an overall safety assessment.