Infection control practices in Europe and the USA have been influenced and shaped over the last 50 years by various technological developments, historical experiences and research schools that have led to different approaches to the control and prevention of healthcare-associated infections. This narrative review attempts to answer the question: Which are the most useful lessons to be learned from this historical experience, as well as methods and measures advocated on both sides of the Atlantic, in order to determine best practices to control and prevent healthcare-associated infections and antimicrobial resistance? The review is intended neither as an expansion of ongoing debates on controversial scientific issues, nor as a complete historical review of modern hospital epidemiology, but should be considered rather a personal viewpoint that tries to bridge the gap between US-influenced hospital epidemiology and traditional microbiology-based hygiene in Europe.