 The article discusses the growing concern of hospital-acquired infections caused by drug-resistant strains of Pseudomonas aeruginosa in critically ill and immunocompromised patients and highlights the need for novel anti-infectives to combat this issue. The review covers various strategies such as killing and disarming the pathogen, risk factors for resistance, mechanisms associated with resistance, clinical approaches to treating P aeruginosa infections, antibiotic combinations, pharmacokokinetic and pharmacodynamic parameters, limitations of current therapies, potential alternative drugs, and new therapeutic options. This article was authored by Matteo Bassetti, Antonio Vina, Anthony Croxato, and others.