Osteoporosis, defined as diminished bone mass, which predisposes the skeleton to fracture with minimal or no trauma, is a major health problem in the United States, affecting an estimated 20 million people. Achievement of peak bone mass in the first three decades of life through adequate nutrition and exercise is considered essential for prevention. Once osteoporosis is established as a disease entity, a variety of medical therapies have proven efficacy. Sex hormone replacement in the estrogen- or testosterone-deficient patient can maintain and in certain cases augment skeletal mass and reduce fracture incidence. The benefits of cyclical estrogen therapy are of limited duration and risks of accelerating the growth of established breast cancer have not been defined. The route of administration may affect the risk to benefit ratio of estrogen on cardiovascular disease morbidity and mortality. Calcitonin is effective in preserving bone mass for a short duration (18 months); the long-term effects, especially on fracture rate, are unknown. The benefits of a number of agents including vitamin D, thiazides, and bisphosphonates are unproven. Agents with apparent benefit, such as fluoride, can produce abnormal bone and may protect select regions (spine) while increasing the risk of fracture in others (hip). New and established medical treatments are evolving that provide hope for safer, more effective therapies.