Hydrogenases are ubiquitous in ecosystems and widespread in microorganisms. In bacteria, hydrogen metabolism is a facultative trait that is tightly regulated in response to both external factors (e.g. gas concentrations) and internal factors (e.g. redox state). Here we consider how environmental and pathogenic bacteria regulate [NiFe]-hydrogenases to adapt to chemical changes and meet physiological needs. We introduce this concept by exploring how Ralstonia eutropha switches between heterotrophic and lithotrophic growth modes by sensing hydrogen and electron availability. The regulation and integration of hydrogen metabolism in the virulence of Salmonella enterica and Helicobacter pylori, persistence of mycobacteria and streptomycetes, and differentiation of filamentous cyanobacteria are subsequently discussed. We also consider how these findings are extendable to other systems.