The genus Burkholderia contains over 30 species, many of which are important human pathogens. In addition to the primary pathogens Burkholderia pseudomallei and Burkholderia mallei, several species have emerged as opportunistic pathogens in persons suffering from cystic fibrosis (CF) and immunocompromised individuals. All Burkholderia species investigated so far employ quorum-sensing (QS) systems that rely on N-acyl-homoserine lactone (AHL) signal molecules to express certain phenotypic traits in a population density-dependent manner. Whilst many Burkholderia strains only contain the CepI/CepR QS system, which relies on C8-HSL, some strains, in particular isolates of B. pseudomallei and B. mallei, harbour multiple LuxI/LuxR homologues and produce numerous AHL signal molecules. Evidence has accumulated over the past few years that the QS systems operating in Burkholderia are crucial for full virulence in various animal models. However, only few QS-regulated functions required for virulence in the different infection models have so far been identified. Given the essential role of QS in the expression of pathogenic traits in Burkholderia these regulatory systems represent attractive targets for the development of novel therapeutics.