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The accelerating rise of multi-drug resistance and resultant difficulties in the treatment of Pseudomonas aeruginosa infections are a significant cause of high morbidity and mortality in infected patients. Antimicrobial resistance resulting from biofilm contributes to a significant disease burden on public health and P.aeruginosa serves as a model for investigating biofilm development. Biofilm makes slime layer over various surfaces (epithelial layer, contact lenses, human teeth, urinary catheters, rocks) and when bacteria break away from the complex aggregation; are a source of serious healthcare-associated infections that are mainly systemic. Biofilm is a significant characteristic of about 99% of bacterial species and serves as a resistive and protective barrier from varied antibiotics. Biofilm communities form pillar-like structures. About 10% of Pseudomonas aeruginosa strains are resistant to antibiotics and account for 8% of urinary tract and pneumonia disorders. Resistance is achieved by numerous phenomena such as reducing outer membrane permeability, using an efflux pump, specialized enzymatical activity, biofilm formation, horizontal resistive-gene transfer, mutations, etc. In this study, we evaluated biofilm from every aspect 1) related to its formation, factors impacting its formation, and its role in antibiotic resistance especially in Pseudomonas. 2) Mechanisms through which P.aeroginosa illustrates intrinsic, adaptive as well as acquired resistance toward antibiotics. 3) Furthermore, the modern antibiotics to treat these resistive strains are also overviewed. Recently, novel therapeutic approaches have played a significant role in the treatment of resistive strains and may include non-antibiotic approaches or may be used with modern antibiotics to be more effective.