The vast industrial use of nickel has led to environmental pollution by the metal and its by-products during production, recycling, and disposal. Nickel is a known hematotoxic, immunotoxic, hepatotoxic, pulmotoxic, and nephrotoxic agent. Allergic skin reactions are common in individuals who are sensitive to nickel. This article presents a selective review on nickel and its effect on certain metabolically active peripheral tissues of human and animals. The subtopics include nickel sources and uses, exposure pathways, transport, excretion, general health effects, and specific acute and chronic nickel toxicities in peripheral tissues like liver, lungs, and kidneys. The review particularly addresses the nickel-induced generation of reactive oxygen species and increased lipid peroxidation in various metabolically active tissues in humans and animals, and the possible role of vitamin c as a protective antioxidant.