There has been excessive rate of use of antibiotics to fight Pseudomonas aeruginosa (P. aeruginosa) infections worldwide, which has consequently caused the increased resistance to multiple antibiotics in this pathogen. Due to the widespread resistance and the current poor effect of antibiotics consumed to treat P. aeruginosa infections, finding some novel alternative therapeutic methods are necessary for the treatment of infections. The P. aeruginosa biofilms can cause severe infections leading to the increased antibiotic resistance and mortality rate among the patients. In this regard, there are no approaches that can efficiently manage these infections; therefore, novel and effective antimicrobial and antibiofilm agents are needed to control and treat these bacterial infections. Quorum sensing inhibitors (QSIs) or quorum quenchings (QQs) are now considered as potential therapeutic alternatives and/or adjuvants to the current failing antibiotics, which can control the virulence traits of the pathogens, so as a result, the host immune system can quickly eliminate bacteria. Thus, the aims of this review article were presenting a brief explanation of the research reports on the natural and synthetic QSIs of P. aeruginosa, and the assessment of the current understanding on the QS mechanisms and various QQ strategies in P. aeruginosa.