Forty years ago, antibiotics and vaccination appeared to have consigned infectious diseases to medical history. Today, some authorities estimate that in 40-years' time deaths due to antibiotic resistant infection could exceed deaths from all other causes combined. In my lecture, I will discuss how this came about. How ‘opportunist’ bacteria such as Staph aureus, Clostridium difficile and E. coli have taken the opportunities created by modern medicine. I will introduce two very different areas of research which are underway to counter this threat. First, microbial whole genome sequencing, which is providing us with extraordinary insights into how these organisms cause disease. Second, optimization of antibiotic use, which is essential if we are to preserve the antibiotics we have now and avoid squandering antibiotics of the future. My experience of clinical research has taught me the importance of keeping what Pasteur called ‘a prepared mind’. By grasping the opportunities presented by practice in this ever-changing field, clinical academics can make vital contributions to tackling the opportunists which threaten modern medicine.