Health care-associated infections are a major public health concern both in the United States and abroad, contributing to increased morbidity, mortality, and health care costs. As a consequence of changes in health care delivery and increasing demands on infection prevention, targeted surveillance has become common in the United States, focusing on areas of the hospital where a patient's risk for health care-associated infection is greatest, as opposed to hospital-wide surveillance; the latter can be used to estimate the national burden of health care-associated infections. Many countries have shown that prevalence surveys can be used to quantify the burden of disease and to help establish priorities to accomplish national goals of prevention of health care-associated infection. Several different surveillance methods have been used, prohibiting comparisons of results among methods. We address some of these key differences and provide recommendations in areas that should be considered when designing a point prevalence survey in the United States.