Nearly a decade since the publication of the WHO Global Strategy for the Control of Antimicrobial Resistance, the World Health Organization has declared this issue as the theme for World Health Day 2011. Antimicrobial resistance is a serious problem that affects the core of infectious disease control efforts and has the potential to hinder progress, and possibly even reverse it. Resistance is a natural response of microorganisms, but can be controlled through the prudent and appropriate use of antibiotics. A multi-pronged approach in well-regulated, integrated health systems in Western European countries has reduced antimicrobial resistance in some pathogenic bacteria. Antimicrobial resistance has been shown to be controlled through integrated monitoring of antibiotic consumption and resistance, government-coordinated and paid prescriber and consumer education, and regulation of antibiotic use in the community and in hospitals. Unfortunately, even in well-regulated systems such as those in Europe, resistance continues to develop unchecked in some pathogenic bacteria, and antibiotic use remains problematic outside of the health system, particularly in veterinary medicine. What is the situation in the developing world where controls are much weaker, diagnostic breakdowns are lacking, and comprehensive health care is a distant expectation? Imperfect health services, largely provided by a profit-driven private sector, leave antibiotics vulnerable to misuse and abuse. Given poor surveillance, the true scale of antimicrobial resistance is likely unknown, and only “shooting stars” like NDM-1 have drawn attention to the problem. There is ample scientific knowledge on the appropriate use of antibiotics. Specific antibiotics are effective only for specific organisms, must be administered at specific doses over a defined period of time, and are ineffective against viral infections. What, then, drives behavior that runs counter to this evidence? There is a misconception that antibiotics are effective for all infections. For many patients, this seems to be the case – patients with viral respiratory infections get better after taking amoxicillin. This is usually the result of the natural course of the disease rather than the effect of amoxicillin (patients may consider the side effect of antibiotics causing diarrhea to be a symptom of the disease). Although good clinical trials have shown that antibiotics have no preventive value, physicians prescribe antibiotics to prevent possible secondary viral infections in patients who are otherwise healthy except for simple viral infections. In the developing world, pharmacies sell antibiotics without a prescription because their revenues depend on sales, not fees or wages for professional services. Pharmaceutical companies may promote antibiotics without regard to the needs of patients. Finally, most antibiotics are susceptible to abuse because of their safety profile and shorter course of treatment; patients often self-administer antibiotics, while few self-administer antihypertensives. Countering these behaviors in an environment of poor health care infrastructure, limited control, and lack of health education is a whole new challenge. Repeated calls for improved drug control must not impede appropriate access; in low- and middle-income countries, antibiotic use will continue to evolve to meet the needs created by lack of access to care. Increased use must be combined with rational use. If access is improved without significant improvements in appropriate use, there will be dire consequences, with a steady stream of “superbugs” and untreatable infections. Fortunately, improving appropriate use of antibiotics often reduces health costs because most of the antibiotics used in most communities are unnecessary. Controlling antimicrobial resistance is the theme of World Health Day 2011. The World Health Organization is developing a comprehensive policy package for ministries of health that targets almost all stakeholders. This will be an opportunity to initiate sustainable actions to control resistance, to use electronic media to raise awareness and education, and to track and control the spread of resistance through the development and use of clinical diagnostics, improved information technology and better support for clinical decisions.