Resistance to antimicrobial agents is emerging in a wide variety of pathogens, particularly those that cause nosocomial infections. As a consequence of this increasing resistance, morbidity and mortality in nosocomial infections is also increasing. It is therefore critical to treat nosocomial infections appropriately by starting antimicrobial treatment early in the course of infection, using the correct agent, at the most appropriate dose, and for an adequate duration. Indeed, early 'appropriate' antibiotic prescribing has been shown significantly to reduce mortality, length of intensive care unit and hospital stay and overall costs. Early use of the correct antibiotic at the appropriate dose and for an adequate duration are key to initial appropriate antibiotic prescribing. Choosing the right antibiotic depends mainly on the likely pathogen(s) and the expected local susceptibility patterns. Selection of appropriate antimicrobial therapy requires a thorough understanding of the likely microbial cause of the infection, including local susceptibility patterns, as well as the properties of the antimicrobials available for treating these infections, namely spectrum of activity and potency (including activity versus known resistance mechanisms), pharmacokinetic profile and tolerability and safety. This review, based on a series of presentations at the 5th International Conference of the Hospital Infection Society (Edinburgh, 2002) examines the importance of appropriate antimicrobial therapy in nosocomial infections, and provides guidance on how to achieve this.