Organisms causing nosocomial infection are frequently resistant to antimicrobial agents. Studies of the reasons for this have been hindered by difficulties in defining terms, by selection biases, by artifacts produced by study methods, and by failure to control for confounding variables. Major factors leading to increased prevalence of resistant organisms in hospitals are changes in organisms causing nosocomial infection (due in part to changes in characteristics of hospital populations and in procedures and instruments used in patient care), increasing prevalence of resistance in bacteria causing community-acquired infection, and use of antimicrobial agents. A causal relationship between antibiotic usage and resistance of hospital organisms is supported by consistent association and concurrent variation in several populations, presence of a doseresponse pattern, and existence of a reasonable biologic model to explain the relationship. Major influences on emergence of resistant hospital bacteria include antimicrobial effects in treated individuals, mechanisms for transfer of resistance between bacteria, and routes of transmission within the hospital for bacteria or their resistance factors. Barrier isolation techniques can help control resistant hospital bacteria. However~ virtually all reports agree that careful, discriminating use of antimicrobial agents remains the keystone for minimizing this problem. This need must be communicated more effectively to prescribers.