The era of antimicrobial therapy is now in its seventh decade. The major scientific discoveries made during this period have saved of countless lives and markedly reduced the morbidity of infectious diseases. These achievements are now threatened by the global emergence of resistant strains. The process is fostered by the remarkable genetic diversity and transfer of resistance among microbes, the selective forces of antibiotic use, and powerful socioeconomic and marketing forces. It is doubtful that development of new drugs will adequately address the problem. The only measures which might slow the development and transmission of resistant microorganisms are those that decrease the global burden of infectious diseases. This requires improved sanitation, nutrition and immunization, hospital infection control and strategies that will diminish the inappropriate and excessive promotion and use of antibiotics. Physicians, pharmacists and consumers need to be better informed about how to use antibiotics and the dangers of inappropriate use. The multinational and local pharmaceutical companies must become more responsible for their products and promotional practices. The current situation is bleak. It will undoubtedly will get worse as the burden of resistant microorganisms continues to increase.