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Bacterial quorum sensing (QS) system is a unique target for the development of a new class of drugs that potentially control pathogenicity and attenuate virulence. Thus, it has been of significant interest to discover small organic molecules that modulate QS circuits by competing with the signaling molecules, or so-called autoinducers (AIs), for binding to QS proteins. In this chapter, we summarize synthetic methodology for custom QS agonists and antagonists against the Lux system in Gram-negative bacteria.