Pseudomonas aeruginosa is an opportunistic pathogen responsible for ventilator-acquired pneumonia, acute lower respiratory tract infections in immunocompromised patients and chronic respiratory infections in cystic fibrosis patients. High incidence, infection severity and increasing resistance characterize P. aeruginosa infections, highlighting the need for new therapeutic options. One such option is to target the many pathogenic mechanisms conferred to P. aeruginosa by its large genome encoding many different virulence factors. This article reviews the pathogenic mechanisms and potential therapies targeting these mechanisms in P. aeruginosa respiratory infections.