It is increasingly recognized that exposure to chemical, nutritional, and behavioral factors alters gene expression and affects health and disease by not only mutating promoter and coding regions of genes, but also by modifying the epigenome — modifications to DNA that confer an additional layer of heritable gene regulation that lead to disease when deregulated. Using examples from animal models, human clinical samples, and human population studies we will examine how many common compounds, such as bisphenol A (BPA), plasticizers, and metals, may have deleterious consequences through abnormal epigenetic and genetic regulation. We will also discuss how unlike genetic mutations, which are static and non-modifiable, epigenetic programming is dynamic and potentially modifiable, allowing for intervention approaches to improve health.