Osteoporosis is a common disease characterized by low bone mass, microarchitectural deterioration of bone tissue and an increased risk of fracture. Population-based and case-control studies have identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, including the vitamin D receptor (VDR), estrogen receptor (ER), oestrogen α receptor (ESR), transforming growth factor (TGF)-β, and type I collagen. The Wnt signaling and receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathways have been shown to play critical roles in determining bone mass and strength. An important aim of future work will be to further clarify the mechanisms involved in the interaction between candidate genes and environmental variables leading to osteoporosis via signaling pathways in individual patients. Hence preventative therapy, particularly gene therapy, could be targeted in patients at greatest risk of osteoporosis.