Pseudomonas aeruginosa is a pathogenic bacterial species that causes infections and diseases in both plants and animals, including several human diseases, especially in immune-compromised patients, and many hospital-acquired infections. Given that P. aeruginosa is an opportunistic pathogen, the occurrence of antimicrobial resistance makes it difficult to treat and eradicate. Antimicrobial resistance in P. aeruginosa is categorized as intrinsic, acquired, or adaptive. Here, we different aspects of resistance and pathogenicity in P. aeruginosa, such as the role of outer membrane proteins, transcriptional regulators, efflux pumps, enzymes, and biofilms in antimicrobial resistance. We also highlight quorum-sensing (QS) genes, their protein secretion, and role in pathogenicity; different QS inhibitors; and the influence of QS on the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system and virulence factor production.