L. pneumophila adopts a biphasic life style and switches between a replicative/ non-motile and a virulent/ transmissive phase. The bacteria employ the α-hydroxyketone LAI-1 (Legionella autoinducer-1; 3-hydroxypentadecan-4-one) for cell-cell communication. LAI-1 is synthesized and detected by the Lqs (Legionella quorum sensing) system comprising the autoinducer synthase LqsA, the sensor kinase LqsS and the response regulator LqsR encoded by the lqs gene cluster, as well as an orphan LqsS homologue termed LqsT. The LAI-1 circuit regulates pathogen-host cell interactions, natural competence, extracellular filaments and a genomic “fitness island”. Recent biochemical experiments indicate that phosphorylation signaling through the sensor kinases LqsS and LqsT converges on LqsR, which catalyzes the dephosphorylation of the phospho-kinases. Moreover, synthetic LAI-1 promotes the motility of L. pneumophila and triggers trans-kingdom signaling by inhibiting the migration of eukaryotic cells.