The marine bacterium Vibrio harveyi possesses two quorum sensing systems (System 1 and System 2) that regulate bioluminescence. Although the Vibrio cholerae genome sequence reveals that a V. harveyi-like System 2 exists, it does not predict the existence of a V. harveyi-like System 1 or any obvious quorum sensing-controlled target genes. In this report we identify and characterize the genes encoding an additional V. cholerae autoinducer synthase and its cognate sensor. Analysis of double mutants indicates that a third as yet unidentified sensory circuit exists in V. cholerae. This quorum sensing apparatus is unusually complex, as it is composed of at least three parallel signaling channels. We show that in V. cholerae these communication systems converge to control virulence.