Legionella pneumophila is a water-borne opportunistic pathogen causing a life-threatening pneumonia called 'Legionnaires' disease'. The Legionella quorum sensing (Lqs) system produces and responds to the α-hydroxyketone signaling molecule 3-hydroxypentadecane-4-one (Legionella autoinducer-1, LAI-1). The Lqs system controls the switch between the replicative/non-virulent and the transmissive/virulent phase of L. pneumophila, and it is a major regulator of natural competence, motility and virulence of the pathogen. Yet, beyond gene regulation, LAI-1 also directly affects pathogen-host interactions, since the signaling molecule modulates the migration of eukaryotic cells. Genes encoding Lqs homologues are present in many environmental bacteria, suggesting that α-hydroxyketone signaling is widely used for inter-bacterial as well as inter-kingdom signaling. In this review we summarize recent advances on the characterization of the Lqs system and its role in L. pneumophila-host cell interactions.