Within the biofilm, the bacteria use cell-to-cell communication systems to pool their activities and act in a multicellular organized manner. One such activity is to launch their arsenal of virulence factors at the strategically right moment, and hence coordinate the progressive attack on the host. This process is termed quorum sensing (QS), whereby bacteria produce diffusible chemical signals (autoinducers) that interact with specific receptors on itself and on neighboring cells, which in turn regulate the expression of specific target genes. By integrating this with other environmental stimuli, bacteria are capable of exhibiting complex responses and take part in sophisticated interactions, allowing them to survive in most adverse environments. This chapter describes the molecular mechanisms of QS in Gram-negative and gram positive bacteria, and QS in a biofilm, leading to what is described in subsequent chapters that QS is a highly attractive target for therapy against biofilm chronic infections.