Remarkable progress has been made during the last 2 decades in understanding telomere biology at the molecular and cellular levels. Clinical epidemiology research of human telomeres, in contrast, is a discipline just coming into its own. The most important observation in studying human telomere biology is that telomere length is highly variable among humans. Here we explain some of the reasons for this variability and propose several principles that should be considered in conducting epidemiological telomere research. Ignoring these principles could lead to misleading conclusions.