The age of antibiotic prophylaxis may be receding into its twilight years because the assumption upon which it was based has not proved generally true. Although antibiotics treat infections, limited benefit has been demonstrated in preventing infections. These are two entirely different biologic entities, a distinction which appears to have gone unappreciated by many for more than 50 years. If the principles of antibiotic prophylaxis established more than 40 years ago had been assiduously followed, many of its abuses could have been avoided. This may not have stopped our legal colleagues, but it would have been worth an effort on behalf of our patients. It is likely that the massive overuse of antibiotics as litigation prevention has contributed to the global epidemic of antibiotic-resistant micro-organisms and an unknown number of serious adverse effects to the antibiotics themselves. Even with this abuse, much money has still flowed from defendant to plaintiff. Substantial data exist that antibiotics do not prevent bacteremias. The absolute risk rate for bacterial endocarditis after dental treatment even in at-risk patients is very low. Antibiotic prophylaxis for surgical infections requires specific dosing schedules (perioperative surgical prophylaxis) to be successful. Hopefully the difficulties presented herein regarding antibiotic prophylaxis will lead to their more enlightened use in the future.