Chronic lung infections are the major cause of morbidity and mortality in individuals suffering from Cystic Fibrosis. The chronic infections are caused by opportunistic pathogens residing in the CF lungs and are a major medical challenge. Antimicrobial chemotherapy has given rise to an array of bacterial resistance which compels the need for the development of novel therapeutic concepts. Recently it is established that pathogenic species colonize the airways in a stealth manner through cell-density dependent communication within their own population utilizing signal molecules, called quorum sensing (QS). Once a certain concentration of cells has been reached, through the QS system, the pathogens regulate and release virulent factors to the surrounding tissue, causing a variety of infections. Furthermore, interspecies interactions have also demonstrated increase virulence. Upon this discovery, methods to quench cell-to-cell signaling have been proposed in order to attenuate pathogenesis. Natural and synthetic antipathogenic compounds have been developed and investigations using the in-vitro and animal model of infections are ongoing