As far as we know, nickel is non-essential for humans; however, microorganisms, plants, and some animal species require nickel for survival.^1–3  These organisms require a delicate balance of nickel levels – too much can result in toxicity and too little can induce deficiency symptoms. Nickel has been classified as a group 1 carcinogen by IARC and several investigations have documented its toxic effects.^4–11  This chapter will focus on the toxicity of nickel and describe data establishing it as a carcinogen. Since nickel is a weak mutagen, its carcinogenicity is largely due to its effects on the epigenome. Table 3.1 may be used as a glossary to understand some of the key terms and phrases presented in the chapter.