Carcinogenic metals affect a variety of cellular processes, causing oxidative stress and cancer. The widespread distribution of these metals caused by industrial, residential, agricultural, medical, and technical activities raises concern for adverse environmental and human health effects. Of these metals, chromium (Cr) and its derivatives, including Cr(VI)-induced, are of a public health concern as they cause DNA epigenetic alterations resulting in heritable changes in gene expression. Here, we review and discuss the role of Cr(VI) in epigenetic changes, including DNA methylation, histone modifications, micro-RNA changes, biomarkers of exposure and toxicity, and highlight prevention and intervention strategies to protect susceptible populations from exposure and adverse occupational health effects. Cr(VI) is a ubiquitous toxin linked to cardiovascular, developmental, neurological, and endocrine diseases as well as immunologic disorders and a high number of cancer types in humans following inhalation and skin contact. Cr alters DNA methylation levels as well as global and gene-specific histone posttranslational modifications, emphasizing the importance of considering epigenetics as a possible mechanism underlying Cr(VI) toxicity and cell-transforming ability. Our review shows that determining the levels of Cr(VI) in occupational workers is a crucial first step in shielding health problems, including cancer and other disorders. More clinical and preventative measures are therefore needed to better understand the toxicity and safeguard employees against cancer.