Molecular hydrogen (H(2)) is used as an energy source or a way to deposit excess reducing power by a wide range of microorganisms. Both H(2) oxidation and production are catalysed by hydrogenases. As these metalloenzymes are usually exquisitely O(2) sensitive, H(2) metabolism under aerobic conditions, which is known as O(2)-tolerant H(2) cycling, involves hydrogenases that have undergone structural and catalytic adaptations and requires a dedicated biosynthetic machinery. Here, we discuss recent high-resolution crystal structure analyses of a particular subtype of [NiFe]-hydrogenase that is predominantly found in aerobic or facultative aerobic H(2)-oxidizing bacteria. These data have provided insights into the underlying molecular strategies that allow sustained biological conversion of H(2) in the presence of O(2).