Worldwide chronic arsenic (As) poisoning by arsenic-contaminated groundwater is one of the most threatening public health problems. Chronic inorganic As (inAs) exposure has been associated with various forms of cancers and numerous other pathological effects in humans, collectively known as arsenicosis. Over the past decade, evidence indicated that As-induced epigenetic modifications have a role in the adverse effects on human health. The main objective of this article is to review the evidence on epigenetic modifications induced by arsenicals. The epigenetic components play a crucial role in the regulation of gene expression, at both transcriptional and posttranscriptional levels. We synthesized the large body of existing research on arsenic exposure and epigenetic mechanisms of health outcomes with an emphasis on recent publications. Changes in patterns of DNA methylation, histone posttranslational modifications, and microRNAs have been repeatedly observed after inAs exposure in laboratory studies and in studies of human populations. Such alterations have the potential to disturb cellular homeostasis, resulting in the modulation of key pathways in the As-induced carcinogenesis. The present article reviews recent data on As-induced epigenetic effects and concludes that it is time for heightened awareness of pathogenic arsenic exposure, particularly for pregnant women and children, given the potential for a long-lasting disturbed cellular homeostasis.