Antimicrobials have been used successfully for over 6 decades, but genes expressing resistance to them have emerged in strains of bacteria and have disseminated through the global ecosystem to reach infecting microorganisms, produce disease, and seriously interfere with therapy, allowing infections to progress and kill despite antibiotic administration. The upsurge in prevalence of such resistance genes in the bacterial population that colonize and infect humans involves two processes, emergence and dissemination, in both of which there have been contributions from the developing world, where resistance is common and increasing. The emergence of pneumococcal isolates noted in Papua New Guinea and later in South Africa that 1 decade later spread to most of the world and the intercontinental spread between the United States and Venezuela of a new gentamicin resistance gene carried on an epidemic plasmid are examples of the ability of bacteria to travel freely, without regard to borders. Complex societal issues such as the misuse of antibiotics by physicians, pharmacists, and the public; the suboptimal quality of the drugs (emergence); and conditions such as crowding, lack of hygiene, poor or nonexistent hospital infection control practices, or insufficient surveillance (dissemination) play a largely unmeasured role that requires study and solutions. In the meantime, we may intervene to delay the emergence of resistance and to limit its spread by promoting the judicious use of antibiotics both at the local level as well as from multinational organized cooperative efforts. Education and improvement of surveillance and socioeconomic conditions are integral parts of any solution strategy.