Biomonitoring, the measurement of chemicals in blood, urine, and other tissues or fluids, is becoming an increasingly common tool in the study of human exposure to environmental chemicals and the potential health effects of those chemicals. The National Health and Nutrition Examination Survey (NHANES) now includes biomonitoring data for hundreds of chemicals as well as information on other health and demographic endpoints for thousands of individuals in the United States. The NHANES databases provide valuable information for deriving reference ranges and trend information and can be used for hypothesis-generating analyses, but they cannot be used to establish causal relationships between environmental chemicals and health effects. This commentary examines issues unique to the use of such databases and the interpretation of biomonitoring-based epidemiological studies.