Superoxide dismutases (SODs) are one of the oldest topics in bioinorganic chemistry, having begun with the discovery of SOD activity and its association with a Cu containing protein in 1969 by McCord and Fridovich.¹  This was rapidly followed by the characterization of MnSOD²  and FeSOD³  in Escherichia coli, and all three metal variants have since been found in various organisms in all three of the families of life: archaea, bacteria, and eukarya.⁴  The most recently discovered SOD is one that requires nickel in its active site – NiSOD. This unusual redox metalloenzyme and the adaptations required to support SOD catalysis by nickel are the main thrust of this chapter.