Arsenic occurs naturally in many environmental components and enters the human body through several exposure pathways. Natural enrichment of arsenic may result in considerable contamination of soil, water, and air. Arsenic in groundwater can exceed values hundreds of time higher than the concentration recommended for drinking water. Such exposure levels indicate a serious potential health risk to individuals consuming raw groundwater. Human activities that have an impact on the environment may increase the distribution of inorganic arsenic. Abandoned mines are of great concern due to the extremely high arsenic concentrations detected in mine drainage and tailings. Diet, drinking water, air, soil, and occupational exposures are all sources of inorganic arsenic for humans. Interdisciplinary efforts to better characterize the transport of arsenic and reactants that facilitate their release to the environment are important for human health studies. Multi-disciplinary efforts are needed to study diet, infectious disease, genetics, and cultural practices unique to each region to better understand human health risk and to design public health interventions.