Most pathogenic bacteria encounter changing growth conditions during their infectious cycle and, accordingly, have to modulate gene expression to enable the efficient colonization of different environments outside or within their host organisms. In Bordetella pertussis the transcription of most virulence factors including several toxins and adhesins is regulated coordinately by the BvgAS two-component system. The molecular characterization of the BvgAS system revealed that it belongs to the small group of unorthodox two-component systems applying an obligate multistep phosphorelay. Moreover, despite the coordinated control of the virulence regulon, subtle differences in the regulation of individual virulence genes were observed which led to the identification of sophisticated mechanisms possibly engaged in fine tuning of virulence gene expression.