If asked to list the greatest advances of modern medicine in order of priority, many—both medical and lay—would put antibiotics at the top of their list. It is surprising therefore that so much of our use of these drugs is based on inadequate evidence and clinical “hearsay”. Nowhere is this more true than their use in prophylaxis against infection. This is particularly unfortunate as such use is complicated by concerns about the promotion of microbial resistance and, in some instances, about the side effects of long term drug administration and about poor compliance. Bacterial resistance to antibiotics is becoming a major issue in both hospital and community practice and has implications not only for the individual patient but also for the community at large. Nevertheless, patterns of treatment have become established and because of the belief, often correct one suspects, that patients would be at risk without them, it has often become difficult to seek objective evidence through placebo controlled trials. This paper examines some of these patterns of use and the evidence, such as it is, to support them. It covers short course prophylaxis first, then long term use, but not the ever changing field of prophylaxis against malaria in travellers1 or the complex field of prevention of infection in children with malignant disease or following bone marrow or organ transplantation.