Despite the enormous progress that has been made in the last few decades in the field of drug design as well as virulence of pathogenic bacteria, the gradual spread of drug resistance can be observed. Only two new classes of antibiotics have been brought to medicine in the last 30 years. The need for novel antibacterial drugs is especially pressing when considering infections caused by multidrug-resistant (MDR) pathogens such as Pseudomonas aeruginosa. The discovery and development of new anti-pseudomonal therapies is one of the main challenges of modern pharmaceutical sciences. The great variety of innovative approaches presented in the current literature is astonishing. In this review, modern, promising strategies against P. aeruginosa infections are described. Antimicrobials, including new antibiotics, β-lactamase and efflux pump inhibitors, quorum quenching molecules and nanoparticles with antibacterial activity are currently being intensively studied. Methods of prevention of infection through vaccines, therapeutic antibodies and development of antimicrobial peptides are discussed as approaches that support the human immunological system. Finally, development of alternative/ supportive therapies such as phage therapy and photodynamic therapy, in which the mechanism of action is completely different from current antibiotic therapy, is of great importance.