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Although most reviews of Pseudomonas aeruginosa therapeutics focus on antibiotics currently in use or in the pipeline, we review evolving translational strategies aimed at using virulence factor antagonists as adjunctive therapies.Current literature regarding P. aeruginosa virulence determinants and approaches that target them, with an emphasis on type III secretion, quorum-sensing, biofilms, and flagella.P. aeruginosa remains one of the most important pathogens in nosocomial infections, with high associated morbidity and mortality. Its predilection to develop resistance to antibiotics and expression of multiple virulence factors contributes to the frequent ineffectiveness of current therapies. Among the many P. aeruginosa virulence determinants that impact infections, type III secretion, quorum sensing, biofilm formation, and flagella have been the focus on much recent investigation. Here we review how increased understanding of these important bacterial structures and processes has enabled the development of novel approaches to inhibit each. These promising translational strategies may lead to the development of adjunctive therapies capable of improving outcomes.Adjuvant therapies directed against virulence factors have the potential to improve outcomes in P. aeruginosa infections.