The Nurses' Health Study was designed as a prospective follow-up study to examine relations between contraception and breast cancer. With follow-up questionnaires mailed every 2 years, investigators have added extensive details of lifestyle practices. The study, currently in its 20th year, has maintained high follow-up with > 90% of participants responding to each of the follow-up cycles since 1988. The relations between use of hormones, diet, exercise, and other lifestyle practices have been related to the development of a wide range of chronic illnesses among women. This review describes the methods used to follow up the study participants and summarizes the major findings that have been described over the first 20 years of the study. We highlight additional areas added to the study in recent years to address emerging issues in women's health. Special emphasis is placed on the recent findings from the study, including relations between weight gain and heart disease, diabetes, and mortality, the lack of relation between calcium and osteoporotic fractures, and the positive relation between postmenopausal use of hormones and risk of breast cancer.