Women may choose to initiate, reinitiate, or discontinue hormone replacement therapy (HRT) at any time beyond the perimenopausal period. HRT, exercise, and nutrition are reviewed in terms of their potential benefits as primary and secondary preventive therapies against coronary heart disease, osteoporosis, breast and genital cancers, and the maintenance of cognitive function among older postmenopausal women. Lifestyle alternatives involving nutrition and exercise that offer many of the same benefits as HRT are discussed. Since both pharmacologic and lifestyle interventions offer significant benefit for primary and secondary prevention of disease and disability, each should be offered to women for consideration as they enter the perimenopausal period. Additionally, each can be recommended for initiation even at much older ages and subsequent to adverse health occurrences, such as the experience of breast or genital cancer or a cardiac event. Each should be sustained over the long term. The decision whether to discontinue these interventions among the most elderly will be influenced by other quality of life considerations. © 1998 by the American College of Nurse-Midwives.