Antibiotics are indispensable for the treatment of bacterial infectious diseases, such as bacterial sepsis or pneumonia. Antibiotics also play a central role in many other areas of modern medicine, in particular to protect patients with a weakened immune system (e.g. in cancer therapies, transplantations or surgical interventions). These achievements are now at risk, as more and more bacterial pathogens are resistant to one or even more antibiotics. Infections with multidrug resistant germs can only be treated with the greatest effort – or not at all. At the same time, current research and development is unable to meet the urgent need for new, effective antibiotics. One reason for this is that antibiotic research to date has mainly investigated bacteria under artificial laboratory conditions. In patients, however, fundamentally different conditions exist and bacteria sometimes behave completely differently. Our knowledge about these processes is still very incomplete. The National Center of Competence in Research (NCCR) “AntiResist” is developing new research approaches to better understand biochemical and biophysical processes of bacterial pathogens in infected patients and to simulate them in tissue models. These findings will help to develop new antibiotics faster and to identify completely new, innovative antimicrobial mechanisms and thus contribute to the development of corresponding drugs. Research focuses on four pathogens that cause major problems worldwide. Overall, the NCCR aims to bring about a paradigm shift in antibiotic research with an interdisciplinary approach that brings together research groups from the fields of clinical research, biology, chemistry, engineering and pharmacology. The NCCR “AntiResist” is funded by the Swiss National Science Foundation, and hosted at the University of Basel. The multidisciplinary consortium includes 29 groups from Universities and University Hospitals throughout Switzerland and Ben-Gurion University in Israel.