Display omitted Pseudomonas aeruginosa can utilize various virulence factors necessary for host infection and persistence. These virulence factors include pyocyanin, proteases, exotoxins, 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), phospholipases, and siderophores that enable the bacteria to cause severe infections in immunocompromised individuals. P. aeruginosa falls into the category of nosocomial pathogens that are typically resistant to available antibiotics and therapeutic approaches. P. aeruginosa bio-film formation is a major concern in hospitals because it can cause chronic infection and increase the risk of mortality. Therefore, the development of new strategies to disrupt biofilm formation and improve antibiotic efficacy for the treatment of P. aeruginosa infections is crucial. Anti-biofilm and anti-quorum sensing (QS) activity can be viewed as an anti-virulence approach to control the infectious nature of P. aeruginosa. Inhibition of QS and biofilm formation can be achieved through pharmacological approaches such as phytochemicals and essential oils, which have shown promising results in laboratory studies. A regulatory protein called LasR plays a key role in QS signaling to coordinate gene expression. Designing an antagonist molecule that mimics the natural autoinducer might be the best approach for LasR inhibition. Here we reviewed the mechanism behind antibiotic resistance and alternative approaches to combat the pathogenicity of P. aeruginosa.