People are exposed to arsenic compounds environmentally, occupationally or therapeutically. In some areas, where arsenic is present in high proportions in the drinking water, this exposure represents an important health concern. Chronic exposure to arsenic leads to hyperkeratosis and loss of skin pigmentation, as well as to significant increases of different types of cancer in skin, lung, bladder and liver; in addition, other pathologies, such as vascular diseases, hepatotoxicity and diabetes, have also been related to arsenic exposure. Since high interindividual variability is observed among people exposed to equivalent doses, genetic susceptibility factors have been postulated to be involved. When inorganic arsenic enters into the body it undergoes metabolic conversion, in a process where methylation plays a crucial role. Trivalent forms, both inorganic and organic, are the most toxic and genotoxic and, for this reason, metabolic variations owing to variant alleles in genes involved in such a process have been the aim of several studies. Genes involved in other mechanisms, such as antioxidant defense and DNA-repair lesions, among others, have also been the subject of association studies. A survey of those studies related to individual susceptibility is summarized here. Results with genes involved in folate one-carbon metabolism and in arsenic transport across the cell membrane provide promising data for future studies.