The main problem in the treatment of nosocomial infections is the increasing drug resistance of microorganisms that cause them, limiting the number of effective antibiotics. Pseudomonas aeruginosa bacilli are the cause of many serious hospital-acquired infections occurring primarily in patients within high-risk groups. The most vulnerable are those with weakened immune systems, as well as those with extensive surgical wounds and burn wounds. Infections are usually of the nature of secondary infections, caused by multidrug strains. Due to the high antimicrobial activity, beta-lactams, aminoglycosides and quinolones are drugs commonly used in hospitals, both in prevention and treatment of infections with P. aeruginosa. However, their irrational use is associated with selection and spread of strains resistant to these antibiotics. Resistance of P. aeruginosa to antibiotics is the result of a number of independent co-occurring mechanisms. These are: reducing the membrane permeability, the efflux system, and production of enzymes inactivating and degrading antibiotics. The paper devotes special attention to the determination of resistance mechanisms responsible for this phenomenon.