© 2015 Elsevier Inc. All rights reserved. It is estimated that 200 million people worldwide are at risk of toxic arsenic exposure with an alarmingly higher number of individuals in developing countries already suffering from chronic arsenicosis. The International Agency for Research on Cancer categorized arsenic as a class I human carcinogen. In this chapter, we have summarized several aspects of arsenicosis. This review focuses on the history, epidemiology, clinical findings, histopathology, molecular pathogenesis, and treatment options related to chronic arsenic ingestion. Arsenic is a metalloid found in great abundance within the earth's crust, which easily enters the groundwater following subtle changes in soil pH, temperature, etc. Chronic arsenic ingestion is the most common cause of arsenicosis, which may occur through environmental, occupational, or accidental exposure.Historically, arsenic was used as a medicine for various maladies such as eczema, furuncles, leprosy, lichen rubor, lupus, molluscum contagiosum, pemphigus, psoriasis, syphilis, urticaria, and warts. In modern medicine, arsenic compounds are still used, but only for the treatment of tropical diseases such as African trypanosomiasis and hematologic malignancies including promyelocytic leukemia. Although chronic arsenic poisoning damages many organ systems, it usually first presents in the skin with manifestations including hyperpigmentation, hyperkeratoses, Bowen's disease, squamous cell carcinoma, and basal cell carcinoma. Although there is no reliable histopathological method to distinguish arsenical keratoses from actinic keratoses, some cases of arsenical keratoses demonstrate unique vacuolization of epithelial cells, keratin horn formation, absent solar elastosis, and a chronic dermal lymphocytic infiltrate.An accumulating body of evidence suggests that arsenic causes many of its deleterious health impacts through oxidative and nitrosative stress. The metalloid disrupts multiple signal transduction pathways and effectively promotes carcinogenesis by activating oncogenes, inhibiting tumor suppressors, and upregulating pathways that may invoke cutaneous inflammatory signaling. Currently, there are no standard guidelines for the treatment of chronic arsenicosis. However, symptomatic treatments are based on the assessment of skin biopsies. In summary, the global reach of arsenicosis and its serious threat to human health signal the need for ongoing study and future planning to prevent exposure and improve the health of populations at risk.