Exposure to arsenic (As) in drinking water is a major health concern. More than 100 million individuals are exposed to levels over the current World Health Organization standard of 10 µg/L worldwide. Arsenic is one of the few agents established as a human carcinogen prior to understanding its mechanism of carcinogenicity. OMIC technologies have enabled researchers to utilize agnostic approaches to explore new, unknown mechanisms through which As causes disease in exposed human populations. In this article, we present recent studies in which OMIC technologies have been used to explore differences in human biological samples to identify markers of exposure, disease susceptibility, and effect in As-exposed and/or diseased tissues. Environ. Mol. Mutagen. 54:589-595, 2013. © 2013 Wiley Periodicals, Inc.