This review focuses on the impact of nickel on human health. In particular, the dual nature of nickel as an essential as well as toxic element in nature is described, and the main forms of nickel that can come in contact with living systems from natural sources and anthropogenic activities are discussed. Concomitantly, the main routes of nickel uptake and transport in humans are covered, and the potential dangers that nickel exposure can represent for health are described. In particular, the insurgence of nickel-derived allergies, nickel-induced carcinogenesis as well as infectious diseases caused by human pathogens that rely on nickel-based enzymes to colonize the host are reviewed at different levels, from their macroscopic aspects on human health to the molecular mechanisms underlying these points. Finally, the importance of nickel as a beneficial element for human health, especially being essential for microorganisms that colonize the human guts, is examined.