In any discussion of new antimicrobial agents in the 1990s, a warning and a plea are necessary. The spreading emergence of resistance among bacteria raises concerns for the effectiveness of antimicrobial therapy. Penicillin-resistant pneumococci are probably of most significance in pediatrics and are increasing in frequency, in part related to the use of antimicrobial therapy in young children to treat such infections as otitis media. New practice guidelines have suggested the more limited use of antimicrobial agents in treating serious otitis media. When pediatricians do treat, they should select effective agents. Limiting therapy to brief courses with effective and narrow-spectrum agents may be helpful also. Treating long enough to ensure eradication in serious infections is equally important. Methicillin-resistant S aureus are also increasing and are increasingly a concern in community-acquired infections and nosocomial infections. Using topical agents, such as mupirocin, to treat impetigo and other superficial skin infections can limit exposure to systemic agents and may delay the spread of resistance. Vancomycin-resistant enterococcal infections, an infrequent pediatric problem, are most frightening because no alternative therapies are available. Their occurrence is directly related to use of vancomycin in the communities that are affected. Containing the spread of drug-resistant bacteria will likely require a concerted effort by both physicians and the public. The indiscriminate use of antimicrobial agents to treat non-bacterial infections should be contained. The public must be educated to understand that antimicrobial agents are ineffective against viral infections. In the setting of managed care, educating administrators who make practice decisions that cheaper is not always better will be crucial. The issues of day-care infections and spread of potential pathogens must take on increasing attention and methods to decrease infection sought. Curbing inappropriate use of antimicrobial agents will be as important as learning the nuances between new agents.