Many bacteria are able to use O2 and nitrate as alternative electron acceptors for respiration. Strategies for regulation in response to O2 and nitrate can vary considerably. In the paradigmatic system of E. coli (and γ-proteobacteria), regulation by O2 and nitrate is established by the O2 -sensor FNR and the two-component system NarX-NarL (for nitrate regulation). Expression of narGHJI is regulated by the binding of FNR and NarL to the promoter. A similar strategy by individual regulation in response to O2 and nitrate is verified in many genera by the use of various types of regulators. Otherwise, in the soil bacteria Bacillus subtilis (Firmicutes) and Streptomyces (Actinobacteria), nitrate respiration is subject to anaerobic induction, without direct nitrate induction. In contrast, the NreA-NreB-NreC two-component system of Staphylococcus (Firmicutes) performs joint sensing of O2 and nitrate by interacting O2 and nitrate sensors. The O2 -sensor NreB phosphorylates the response regulator NreC to activate narGHJI expression. NreC-P transmits the signal for anaerobiosis to the promoter. The nitrate sensor NreA modulates NreB function by converting NreB in the absence of nitrate from the kinase to a phosphatase that dephosphorylates NreC-P. Thus, widely different strategies for coordinating the response to O2 and nitrate have evolved in bacteria.