The article provides a historical perspective on the exposure, toxicity, and metabolism of arsenic, a metalloid that is naturally present in the environment and has been used in various human applications. Arsenic has a long history as a homicidal agent and has been used in pesticides, chemotherapy, and consumer products. High levels of arsenic in drinking water pose significant toxicological concerns in some regions. Arsenic exists in both inorganic and organic forms, primarily as trivalent (III) and pentavalent (V) species. Trivalent arsenic is generally more toxic than pentavalent arsenic. Acute effects of arsenic exposure range from gastrointestinal distress to death, while chronic exposure can affect multiple organ systems and increase the risk of cancer, particularly of the skin, bladder, and lung. The metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, involves sequential reduction and oxidative methylation. Understanding the chemistry and metabolism of arsenic is crucial for comprehending its toxicology. The article also discusses the historical use of arsenic in medicine, pigments, and pesticides, as well as its environmental sources and exposure pathways. Research on arsenic metabolism has advanced our understanding of its toxic effects and the role of interindividual variation in susceptibility.The article provides a historical perspective on the exposure, toxicity, and metabolism of arsenic, a metalloid that is naturally present in the environment and has been used in various human applications. Arsenic has a long history as a homicidal agent and has been used in pesticides, chemotherapy, and consumer products. High levels of arsenic in drinking water pose significant toxicological concerns in some regions. Arsenic exists in both inorganic and organic forms, primarily as trivalent (III) and pentavalent (V) species. Trivalent arsenic is generally more toxic than pentavalent arsenic. Acute effects of arsenic exposure range from gastrointestinal distress to death, while chronic exposure can affect multiple organ systems and increase the risk of cancer, particularly of the skin, bladder, and lung. The metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, involves sequential reduction and oxidative methylation. Understanding the chemistry and metabolism of arsenic is crucial for comprehending its toxicology. The article also discusses the historical use of arsenic in medicine, pigments, and pesticides, as well as its environmental sources and exposure pathways. Research on arsenic metabolism has advanced our understanding of its toxic effects and the role of interindividual variation in susceptibility.