Nickel is required for the catalytic activity of several microbial enzymes (see Chapters 5–11 in this book). Although an abundant element on earth as a whole, nickel is present at low concentrations (in the nM range) in most natural habitats in the biosphere (see Chapter 2), and bacteria have developed energy-coupled high-affinity nickel transporters to meet the cell needs.¹  In contrast, some environments, such as serpentine soils and industry-contaminated areas, contain high nickel concentrations (Chapter 2). Overload of nickel ions induces toxicity in microbial cells through mismetallation of metalloenzymes, spurious binding to enzymes in active site or in other sites, and indirect oxidative stress (see ref. 2 and Chapter 3), and microorganisms thriving in these habitats use nickel efflux systems to balance unspecific nickel entry into the cytoplasm.¹  Intracellular levels of free nickel ions are kept to virtually zero, due to the presence of nickel chaperone/storage histidine rich proteins in different nickel metalloenzyme biosynthetic systems.³  In addition, highly sensitive nickel-responsive regulators maintain a precise homeostasis of this element by translating the cellular level of Ni(ii) into the expression of proteins devoted to modulating nickel uptake, efflux, and cellular utilization even in normal, low-nickel habitats (see ref. 4 and Chapters 13 and 14).