SummaryOne of the major challenges for modern medicine is our ageing society and an increased level of immunocompromised hosts. More invasive and intensive medical interventions will increase the number of healthcare-associated infections (HCAI), which means infection that occur because of or in concomitance, but in any case, during or after healthcare interventions. Such infections are caused usually endogenously from microbial components of the patient’s own microbiome. Usually, the microorganisms of the microbiome show a natural resistance against a few antibiotics. Due to selection processes and epidemic transmission of specific clones, microorganisms that have become resistant to multiple antibiotics become part of the patient’s microbiome and can subsequently cause infections that are difficult or even impossible to treat. The kind of infections that will occur depends on diverse factors. Already today, according to Cassini et al., 2,609,911 new cases of HCAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 disability-adjusted life years (DALYs) per 100,000 general population each year in the EU/EEA. In a recent publication, 426,277 healthcare-associated infections caused by antimicrobial resistant microorganisms were calculated to occur in the EU every year. Attributable deaths in the EU due to antimicrobial resistant microorganisms were estimated to be 33,110 per year. We know that we cannot prevent all HCAI. Because medical innovations will allow for an increased number of novel treatments that will comprise abiotic materials, microorganisms will adapt to this environment and enhance the risk for new HCAI. The challenge for the future will not be to try to prevent all infections, as some of them will remain unavoidable, but to prevent the occurrence of non-treatable microorganisms that would make unavoidable infections additionally untreatable. That means that we need to reflect on how we organize infection prevention, diagnostics and control. While patients with classical infectious diseases present with infectious diseases (ID)-specific symptoms, patients with HCAI present usually with another underlying disease. HCAI are therefore perceived as a secondary damage not following classical clinical and epidemiological rules. However, more recently we have to consider how we should react to HCAI and antimicrobial resistance (AMR) as they are quite different in epidemiology and transmission behavior than classical infectious diseases. Today, the prevalence of AMR is rising all over Europe. Although good success has been seen in many countries, methicillin-resistant Staphylococcus aureus (MRSA) remains an important challenge for many countries. In addition to MRSA, multidrug-resistant Escherichia coli and carbapenem-resistant Enterobacteriaceae are becoming a problem of public health importance. Furthermore, we need to focus more on implementation of known infection prevention measures than trying to solve the problem by observing and describing it. However, in addition to medical factors such as antibiotic use, hand hygiene etc., we tend to forget that there are factors behind these factors that have a major influence and are found in the structures of our different healthcare systems. We need to look more at the context before we try to implement prevention measures and need to learn from each other. A common goal to tackle carbapenem-resistant Enterobacteriaceae (CRE) by 2030 would be an important step to foster collaboration across Europe. As the current funding and remmuneration system does not sufficiently support prevention of HCAI and AMR, it is time for the development of a less production- but more prevention-economic financing system for clinical microbiology and infection control.