The lessons of the antibiotic era are crystal clear: in the footrace between humans and microbes, the organisms' genetic repertoire and efficient response to environmental changes will win the day. New antibiotics are essential, but their shelf life will be enhanced only if used wisely and sparingly. The antibiotic era is continually threatened by inappropriate decisions regarding use, inappropriate choices, and unnecessary durations of treatment. In concert with improved prescribing habits, efforts to identify and isolate resistant organisms introduced from outside institutions are essential. Last, continual energy is needed to influence the behavior of health care professionals and to maintain optimal infection control policies and procedures. We remain optimistic about the ability of infectious diseases physicians to respond appropriately to continued microbial challenges with research, education, and wise practice.