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Bone pain occurs following a variety of injuries and diseases including bone fracture, osteoarthritis, low back pain, orthopedic surgery, fibrous dysplasia, rare bone diseases, sickle cell disease and bone cancer. In the past 2 decades, significant progress has been made in understanding the unique population of sensory and sympathetic nerves that innervate bone and the mechanisms that drive bone pain. Following physical injury of bone, mechanotranducers expressed by sensory nerve fibres that innervate bone are activated and sensitized so that even normally non\u2010noxious loading or movement of bone is now being perceived as noxious. Injury of the bone also causes release of factors that; directly excite and sensitize sensory nerve fibres, upregulate proalgesic neurotransmitters, receptors and ion channels expressed by sensory neurons, induce ectopic sprouting of sensory and sympathetic nerve fibres resulting in a hyper\u2010innervation of bone, and central sensitization in the brain that amplifies pain. Many of these mechanisms appear to be involved in driving both nonmalignant and malignant bone pain. Results from human clinical trials suggest that mechanism\u2010based therapies that attenuate one type of bone pain are often effective in attenuating pain in other seemingly unrelated bone diseases. 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