In bacteria, two-component systems (TCS) are widely used signal transduction devices which are engaged in a multitude of gene regulatory systems that respond to changing growth conditions. Many pathogenic bacteria encounter different microenvironments during their infectious cycle and their ability to efficiently adapt to different niches inside and outside of their host organisms is frequently mediated by TCSs, which can, therefore, be considered as an essential prerequisite for their pathogenicity. Although significant progress has been made in the elucidation of basic principles of the signal transduction process itself, in many pathogens the contribution of TCS to bacterial virulence is insufficiently recognized.