The actinobacteria are a group of high-GC Gram-positive bacteria that include many important human, plant, and animal pathogens and are of huge industrial importance. The best-studied genera in the actinobacteria are the corynebacteria, mycobacteria, and streptomycetes. To survive, all bacteria must sense and respond to their environment and one of the major ways in which they do this is via two-component signal transduction pathways. In the classical two-component system model, the extracellular domain of the transmembrane sensor kinase senses a specific signal, autophosphorylates its intracellular kinase domain, and passes that phosphate group to its cognate response regulator. In recent years, it has also become clear that many sensor kinases are bifunctional. This gives the sensor protein much tighter control over the whole signal transduction pathway because, instead of simply phosphorylating its cognate response regulator and letting it go, the sensor kinase can also suppress the levels of phosphorylated response regulator in the absence of signal and switch the pathway off when the signal has disappeared.