Nickel-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen species is reviewed. Nickel is a known haematotoxic, immunotoxic, neurotoxic, genotoxic, reproductive toxic, pulmonary toxic, nephrotoxic , hepatotoxic and carcinogenic agent. This article presents a selective review on nickel and effect of its acute, subchronic and chronic doses on certain metabolically active tissues in human as well as animals. Nickel exposure causes formation of free radicals in various tissues in both human and animals which lead to various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulphydryl homeostasis. The primary route for nickel toxicity is depletion of glutathione and bonding to sulphydryl groups of proteins. Nickel homeostasis, nickel-induced activation of signaling pathways and the protective role of enzymatic and non-enzymatic antioxidants against nickel toxicity and carcinogenicity are also discussed.