Optimal patient care cannot be realized without effectively managing risks related to healthcare-associated infections (HAI). Among human hospital admissions in the United States in 2002, there were approximately 4.5 HAI per 100 admissions, with surgical site infections (SSI) accounting for an estimated 20%, or approximately 2 SSI per 100 procedures. When considering the occurrence of disease in a population, it is important to remember that disease does not occur randomly in populations. Therefore, when thinking about managing risks associated with the occurrence of SSI, consideration should be given to key factors in disease development (the agent, the host, and the environment), and a multifaceted approach to prevention efforts should be considered, including the identification of high-risk populations, adherence to aseptic principles, judicious use of antimicrobial drugs, and surveillance targeting SSI to better inform infection control practices within a facility. Although not all HAI are preventable, it is important to focus efforts on the preventable fraction and to take all reasonable precautions to mitigate foreseeable risks.