Changes to covalent modifications of DNA and histones can be induced via environmental stimuli such as nutrients, hormones and drugs. These changes can be both transient and heritable in nature and provide a framework in which to investigate how environment and lifestyle choices impact disease susceptibility and progression. Furthermore, these modifications are central to chromatin dynamics and, as such, play key roles in many biological processes involving chromatin, such as DNA replication and repair, transcription and development. In this review we provide an overview of recent advances in our understanding of the roles that DNA and histone modification play in the onset and progression of human disease.