The effects of hormone replacement therapy (HRT) on bone cannot be discussed in isolation, and the risks and benefits of therapy must be addressed as they relate to each individual. Hormone replacement therapy has been shown to have a positive impact on bone mineral density (BMD) in all areas of the skeleton that have been studied and has been shown to reduce the risk of osteoporotic fractures. Positive effects of estrogen on the cardiovascular system have also been reported; however, more recently there is evidence to the contrary. The association of unopposed estrogen therapy to uterine cancer is established and it is felt that the addition of a progestational agent reduces that risk. The potential association of estrogen therapy with increased risk of breast cancer remains an area of controversy. However, it is likely that there is a slight increase in risk. HRT unequivocally aids with menopausal symptoms and is the reason most women consider it. Hot flashes, flushes, and urogenital symptoms may be improved with HRT. Recent suggestions that associate improved memory with HRT are encouraging, but require further study. As is evident, the amount of information that needs to be assimilated by both patient and physician is formidable, making the decision to commence HRT a difficult one. This chapter is an attempt to summarize a very complex and changing area.