The Nurses' Health Study, a cohort of 121 701 female registered nurses, was established in 1976 to prospectively address the relationship between the use of oral contraceptives and the risk of breast cancer. Through followup questionnaires every 2 years, exposures have been updated and new exposure assessments added. Repeated measures have allowed a broad range of analyses, including change measures and risk according to time since exposure. Responding to emerging public health issues and accessing new measures (such as exposure to silicone implants, air pollution and the built environment) has allowed investigators to address an evolving spectrum of topics. Prospective data on a wide range of chronic conditions have allowed assessment of preventable fractions of diseases, development of risk prediction models, and other applications that bring data to bear on translation of epidemiologic findings to health policy and practice. The aim of this report is to highlight the features of the Nurses' Health Study and other cohorts that demonstrate continuing contributions to the changing epidemiology of chronic conditions.