Arsenic is ubiquitous and exposure can occur from natural and anthropogenic sources. Human exposure occurs from air, food, and drinking water. Airborne exposure is small except in polluted locations. Food exposure can be significant but, particularly in fish and shellfish, it is mostly in organic forms that are relatively nontoxic. Drinking water remains the most significant source worldwide, and large numbers of people are subject to serious exposure from this source in India, Bangladesh, China, and Mongolia. Toxicity consists mostly of neuropathy, skin lesions, vascular damage, and carcinogenesis. Vascular lesions are the result of endarteritis (blackfoot disease). This appears to be more prevalent in developing rather than developed countries and may be related to nutritional deficiencies. Skin cancer is the most clearly associated malignancy related to arsenic exposure from drinking water; however, bladder, lung, liver, and kidney tumors also appear to be related. Whereas the toxicity of drinking water levels of >200 g/L is well established, the toxicity below 100 g/L is not clearly defined, and this remains one of the most important enigmas in arsenic toxicology today.