concentrations correlated with specific population cell densities, activate their respective regulators thus altering gene expression and coordinating behavior. P. aeruginosa employs five interconnected QS systems – las, rhl, pqs, iqs, and pch – that each produce unique signaling molecules. The las and rhl systems are responsible for the activation of numerous QS-controlled genes, the pqs system is involved in quinolone signaling, and the iqs system plays an important role in intercellular communication. QS in P. aeruginosa is organized in a hierarchical manner. At the top of the signaling hierarchy is the las system, since the las regulator initiates the QS regulatory system by activating the transcription of a number of other regulators, such as rhl. So, the las system defines a hierarchical QS cascade from the las to the rhl regulons. Detection of these molecules indicates P. aeruginosa is growing as biofilm within the lungs of cystic fibrosis patients. The impact of QS and especially las systems on the pathogenicity of P. aeruginosa is unclear, however. Studies have shown that lasR-deficient mutants are associated with more severe outcomes in cystic fibrosis patients and are found in up to 63% of chronically infected cystic fibrosis patients despite impaired QS activity. QS is known to control expression of a number of virulence factors in a hierarchical manner, including the pigment pyocyanin. However, although the las system initiates the regulation of gene expression, its absence does not lead to loss of virulence factors. Recently, it has been demonstrated that the rhl system partially controls las-specific factors, such as proteolytic enzymes responsible for elastolytic and staphylolytic activities, but in a delayed manner. So, las is a direct and indirect regulator of QS-controlled genes. Another form of gene regulation that allows the bacteria to rapidly adapt to surrounding changes is through environmental signaling. Recent studies have discovered anaerobiosis can significantly impact the major regulatory circuit of QS. This important link between QS and anaerobiosis has a significant impact on production of virulence factors of this organism. Garlic experimentally blocks quorum sensing in P. aeruginosa. Biofilms formation and cyclic di-GMP As in most Gram negative bacteria, P. aeruginosa biofilm formation is regulated by one single molecule: cyclic di-GMP. At low cyclic di-GMP concentration, P. aeruginosa has a free-swimming mode of life. But when cyclic di-GMP levels increase, P. aeruginosa start to establish sessile communities on surfaces. The intracellular concentration of cyclic di-GMP increases within seconds when