Osteoporosis is a common condition that is clinically important because of its association with fracture. Fracture risk is ultimately determined by the relation between bone strength and propensity to trauma. Bone density is a key determinant of bone strength, and depends on the bone gained during growth and consolidation, and the subsequent rate of bone loss. Many factors (both genetic and environmental) influence the risk of future fracture through effects on these key intermediary mechanisms. Fracture risk increases greatly with age and is generally higher in women than in men and in whites than in other races. Around 30% to 40% of the variance in peak bone mass is genetically determined, and polymorphisms for several candidate genes are currently being identified. Sex hormone deficiency after the menopause is a key factor in the pathogenesis of osteoporosis in women. In addition, however, there are environmental influences that affect bone density, such as cigarette smoking, alcohol consumption, physical inactivity, and nutrition. Using age, BMD, and other risk factors, it is now possible to identify populations at high risk of osteoporotic fractures. Such populations will potentially derive maximal benefit from therapies and other strategies that reduce fracture risk.