Bacterial pathogens coordinate the expression of multiple virulence factors and formation of biofilms in cell density dependent manner, through a phenomenon named quorum sensing (QS). Protected in the biofilm community, bacterial cells resist the antibiotic treatment and host immune responses, ultimately resulting in difficult to treat infections. The high incidence of biofilm-related infections is a global concern related with increased morbidity and mortality in healthcare facilities, prolonged time of hospitalization and additional financial cost. This has led to the urgent need for innovative strategies to control bacterial diseases and drug resistance. In this review, we outline the disruption of QS pathways as a novel strategy for attenuation of bacterial virulence and prevention of resistant biofilms formation on medical devices and host tissues. Unlike the traditional antibiotics, inhibiting the QS signaling in bacteria will not kill the pathogen or affect its growth, but will block the targeted genes expression, making the cells less virulent and more vulnerable to host immune response and lower dosage of antimicrobials. We summarize the recent successes and failures in the development of novel anti-QS drugs as well as their application in controlling bacterial infections in healthcare facilities. The inhibitory targeting of the production of QS signals, their transduction and recognition by the other cells in the surrounding are discussed. Special focus is also given to the anti-QS nanomaterials with improved effectiveness and specificity towards the pathogens.