The most common chronic disorders are multifactorial in nature, influenced by complex sequences of gene-gene and gene-environment interactions. While gene expression is a dynamic process that varies in response to a myriad of internal and external triggers and the surrounding micro-environment, epigenetic mechanisms play a key role in mediating environmental influences on gene expression and epistatic interactions. In this respect, the expression of complex phenotypes should be assessed in a functional context that examines the interplay between environmental, genetic, and epigenetic factors. Recent advances in genetic and epigenetic research offer new opportunities to integrate experimental approaches, including animal models and in vitro/in vivo translational research, with computational strategies to predict such interactions at multiple levels of complexity. This session focuses on current research investigating the role of genetic factors, epigenetic factors, and gene-environment interactions in the development and outcomes of complex diseases caused by environmental and occupational toxicants.