Molecular hydrogen is widely used by microorganisms as a source of energy. One of the best studied aerobic hydrogen oxidizers, the beta-proteobacterium Ralstonia eutropha (formerly Alcaligenes eutrophus), harbors two distinct [NiFe]-hydrogenases which catalyze the heterolytic cleavage of H2 into 2H+ and 2e-. The genes encoding the hydrogenase subunits are arranged in two large operons together with accessory and regulatory genes involved in hydrogenase biosynthesis. Both operons are transcribed from strong sigma54-dependent promoters. Transcription requires the activation by the HoxA protein, a member of the NtrC family of response regulators. HoxA is only active when H2 is present in the environment. H2 recognition is mediated by a signal transduction complex consisting of the soluble histidine protein kinase HoxJ and a regulatory [NiFe]-hydrogenase which acts as an H2 receptor. Biochemical and genetic data suggest that signal transduction between the RH and HoxJ involves an electron transport process. According to our current model the histidine protein kinase HoxJ inactivates HoxA by phosphorylation in the absence H2. This property of the HoxJ-HoxA regulator pair is quite different from the behaviour of common two-component regulatory systems. Phosphorylation of HoxA is blocked in the presence of H2 provided the RH can contact HoxJ and transmit the signal to the kinase. Furthermore, hydrogenase gene expression is subject to a global regulatory network in response to the carbon and energy source. HoxA is a major component of this epistatic control the molecular mechanism of which is not yet understood.