Genetic factors play an important role in the pathogenesis of osteoporosis--a common condition characterized by reduced bone mass and increased fracture risk. Twin and family studies suggest that up to 85% of the variance in bone mineral density is genetically determined, and molecular genetic studies have identified several candidate genes which may be involved in this process. The vitamin D receptor gene (VDR) has been most widely studied, but the relationship between VDR polymorphisms and bone density is inconsistent, and poorly reproducible in different populations. Polymorphisms in and around other candidate genes have also been associated with bone mass, but the most promising candidate so far identified is the collagen type 1 alpha gene. A polymorphism in the regulatory region of this gene has recently been described which affects a recognition site for the transcription factor Sp1. This polymorphism is associated, not only with bone mass, but also with bone loss and the clinically important condition of osteoporotic fracture. Since osteoporosis is a preventable disease, clinical testing for this and other polymorphisms may have a future role to play in the clinical assessment of osteoporotic fracture risk, along with other diagnostic tools such as biochemical markers of bone turnover and bone densitometry.