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Pseudomonas aeruginosa is a ubiquitous and opportunistic human pathogen that 12 represents a critical problem to the clinician due to the increased number of 13 resistant strains isolated from hospital settings. In addition, there is a great 14 variety of pathologies associated with this versatile Gram-negative bacterium. 15 P. aeruginosa cells are able to produce an incredible arsenal of virulence factors, 16 especially secreted molecules that act singly or together to ensure the 17 establishment, maintenance, and persistence of a successful infection in 18 susceptible hosts. In this context, pseudomonal proteases roles are highlighted 19 due to their ability to cleave key host proteinaceous substrates as well as to 20 modulate several biological processes, for example, escaping and modulating the 21 host immune responses in the bacterial own favor. Proteases secreted by 22 P. aeruginosa include elastase A (LasA), elastase B (LasB), alkaline protease 23 (AP), protease IV (PIV), Pseudomonas small protease (PASP), large protease A 24 (LepA), MucD, and P. aeruginosa aminopeptidase (PAAP). In the present 25 review, we discuss the role of each of these relevant proteases produced by P. aeruginosa taking into consideration their main biological functions in the 27 bacterium–host interaction that favors the establishment of the infectious 28 process