Despite significant progress in our understanding of their pathogenesis, nosocomial infections remain a major problem in hospitals. They may originate from the endogenous flora of the patient as a result of translocation of microorganisms from a physiologically colonized area to an area, where they act as pathogens. Transmission of microorganisms between patients results in exogenous infections. Healthcare workers may serve as transient carriers and vectors or even as reservoir of these infectious agents. Both, exogenous as well as endogenous nosocomial infections are preventable. Based on knowledge of the mode of transmission, the pathogenesis of and risk factors for infection, it is possible to design appropriate preventive strategies, which must be targeted to the type of infection to be prevented and should also be adapted to the local circumstances in a given hospital. Regardless of the type of infection to be prevented, hand disinfection is a standard measure and remains the most important preventive activity. The approach to the prevention of nosocomial infections has to be interdisciplinary and should involve all areas that are affected by any of the proposed measures. Hospital epidemiology plays a central role in coordinating preventive activities and often sets the priorities for prevention based on the available information. Given the growing complexity and the emergence of new nosocomial threats such as SARS, hospital administrators are well advised to invest sufficiently into their department of hospital hygiene and epidemiology in order to be ready for all the problems that will need to be tackled in the future.