Infections with Pseudomonas aeruginosa have become a concerning threat in hospitalacquired infections and for cystic fibrosis patients. The major problem leading to highmortality lies in the appearance of drug-resistant strains. Therefore, a vast number ofapproaches to develop novel anti-infectives is currently pursued. These diverse strategiesspan from killing (new antibiotics) to disarming (anti-virulence) the pathogen. Particularemphasis lies on the development of compounds that inhibit biofilms formed in chronicinfections to restore susceptibility towards antibiotics. Numerous promising results aresummarized in this perspective. Antibiotics with a novel mode of action will be needed toavoid cross resistance against currently used therapeutic agents. Importantly, antivirulence drugs are expected to yield a significantly reduced rate of resistancedevelopment. Most developments are still far from the application. It can however beexpected that combination therapies, also containing anti-virulence agents, will pave theway towards novel treatment options against P. aeruginosa.