Patient factors that contribute to resistance are identified, the concept of the "genesis patient" is explained, and strategies for preventing or overcoming resistance are described. Technology makes it possible to support medically compromised patients. These patients, called genesis patients, cannot clear mutant organisms that develop resistance, and they become focal points for the emergence and spread of resistant organisms. Strategies to control the emergence of resistance in institutional settings must take into consideration the unique role of genesis patients. A wide range of patient- and antibiotic-related factors must be considered. Suboptimal dosing clearly plays a role in the development of resistance. A formulary that seeks to curtail expenses by severely limiting antimicrobial choices may actually drive costs up because it contributes to the emergence of resistance. The best formulary strategy may be to include a wide variety of antimicrobials from all available classes. Particularly in genesis patients, real-time surveillance to ensure timely, effective antimicrobial therapy is essential.