The incidence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections continues to rise in National Nosocomial Infections Surveillance system hospitals, and these pathogens are reportedly causing more than 100,000 infections and many deaths each year in US healthcare facilities. This has led some to insist that control measures are now urgently needed, but several recent articles have suggested that isolation of patients does not work, is not needed, or is unsafe, or that a single cluster-randomized trial could be used to decide such matters. At least 101 studies have reported controlling MRSA infection and 38 have reported controlling VRE infection by means of active detection by surveillance culture and use of isolation for all colonized patients in healthcare settings where the pathogens are epidemic or endemic, in academic and nonacademic hospitals, and in acute care, intensive care, and long-term care settings. MRSA colonization and infection have been controlled to exceedingly low levels in multiple nations and in the state of Western Australia for decades by use of active detection and isolation. Studies suggesting problems with using such data to control MRSA colonization and infection have their own problems, which are discussed. Randomized trials are epidemiologic tools that can sometimes provide erroneous results, and they have not been considered necessary for studying isolation before it is used to control other important infections, such as tuberculosis, smallpox, and severe acute respiratory syndrome. No single epidemiologic study should be considered definitive. One should always weigh all available evidence. Infection with antibiotic-resistant pathogens such as MRSA and VRE is controllable to a low level by active detection and isolation of colonized and infected patients. Effective measures should be used to minimize the morbidity and mortality attributable to these largely preventable infections.