Antibiotic resistance has become a worldwide problem. However, the reasons for the uneven geographic distribution of antibiotic-resistant microorganisms are not fully understood. For instance, there are striking differences in the epidemiology of multiresistant gram-positive cocci between the USA and Germany. According to recent reports, the prevalence of high-level penicillin-resistant pneumococci (PRP), meticillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in clinically relevant isolates of hospitalised patients in the USA and Germany are: PRP, 14% versus less than 1%; MRSA, 36% versus 15%; and VRE, 15% versus 1%. These disparities may be explained by several determinants: (1) diagnostic practice and laboratory recognition (all three pathogens); (2) clonal differences and pathogen transmissibility (VRE); (3) antibiotic prescribing practices (all three pathogens); (4) population characteristics, including extensive daycare exposure in the USA (PRP); (5) cultural factors (all three pathogens); (6) factors related to the health-care and legal system (all three pathogens); and (7) infection-control practices (MRSA and VRE). Understanding these determinants is important for preventing further spread of multiresistant cocci within the USA. A rational approach to national surveillance is urgently needed in Germany to preserve the favourable situation and decrease MRSA transmission. Finally, we suggest that a macro-level perspective on antibiotic resistance can broaden the understanding of this worldwide calamity, and help prevent further dissemination of multiply resistant microorganisms.