The health of organisms from plants to animals to humans depends upon proper epigenetic control. Malfunctions in the epigenetic machinery during development have been linked to several major pathologies in humans, including chromosomal instabilities (e.g., Fragile-X), and mental retardation (e.g., RETT syndrome). There are now compelling human epidemiological and animal experimental data that indicate the risk of developing complex diseases is influenced by persistent epigenetic adaptations in response to early exposures to environmental factors, including toxins, nutrition, and the social environment. Environmental exposures during development may alter the risk of developing medical conditions such as asthma, autism, cancer, cardiovascular disease, diabetes, and obesity by modifying the epigenome. Epigenetic changes during development have also been linked to psychiatric disorders, including schizophrenia, bipolar disorder, and depression. Because epigenetic changes involve modifications to gene function rather than changes to gene sequence, they are potentially reversible, and amenable to therapeutic intervention.