P. aeruginosa, being a leading cause of nosocomial infections,encouraged several studies to discuss its sharing part in hospital-acquiredinfection, clinical impact of multi-drug resistance and mechanisms ofsuch resistance. The present essay highlights the data of drug resistancein Pseudomonas aeruginosa with a special emphasis on types, geneticsand different mechanisms of resistance to understand the emergence,spread, and persistence of antibiotic resistance, and summarizes theoptional treatment feasible for these resistant bacteria.Treatment options for multidrug-resistant P. aeruginosa infectionsare quite limited in most cases. However, immunotherapy is a promisingnew modality being explored. Prevention of emergence of resistancethrough combination therapy and pharmacokinetic strategies are studied.There is presently no reason to doubt that strategies of optimalprescribing, including control of antibiotic use, should be a leadingpriority in the effort to improve therapeutic outcomes in pseudomonalinfections.Finally, it is needless to underline the importance of strict complianceto infection control measures to escape the horizontal transmission ofmultiresistant Pseudomonas clones.