With the rapid process of industrialization and the growth of the human population to unprecedented levels, individuals are increasingly exposed to multiple pollutants known to have an adverse impact upon human health, such as heavy metals, endocrine disruptors, tobacco smoke, polychlorinated biphenyls, diesel exhaust particles, pesticides, and other indoor and outdoor pollutants. Multiple non-communicable diseases (NCDs), including stroke, heart disease, cancers and chronic respiratory disease, now amount to nearly two-thirds of the total deaths caused by unhealthy environments. Considering this global burden, it is vital to understand the mechanisms underpinning the associations between environmental exposures and NCDs. Many studies have demonstrated that the epigenome can be altered by the environmental exposures, but the functional role of these changes in the processes of diseases have not been fully elucidated. This Research Topic has collated high-quality studies in the form of five reviews and four original research papers covering the genetic and epigenetic response to a range of environmental exposures.