Arthritis is a major source of chronic pain, distress and disability, although mechanisms of arthritis pain are incompletely understood, and current treatments often have limited efficacy. In osteoarthritis (OA), subchondral bone marrow lesions (BMLs) seen by magnetic resonance imaging are associated with current pain, and change in parallel with changing pain. Bone marrow lesions reflect diverse histological characteristics, with increases in bone turnover, as well as fibrovascular and inflammatory cell infiltration of bone marrow spaces. These changes are associated with increased osteoclast activity. Interventions that reduce osteoclast activity display analgesic efficacy in OA, both in animal models and in clinical trials. Bisphosphonates reduced pain in people with BMLs in a randomized clinical trial. Osteoprotegerin-Fc reduced pain behaviour in rodent models of OA. Osteoclasts, by reducing pH within the subchondral bone, might facilitate nociceptor activation through pH sensitive ion channels such as TRPV1. Furthermore, osteoclasts express factors that might sensitise nociceptors, and release other pain mediators during matrix degradation. In the medium to long term, structural changes at the osteochondral junction might further contribute to OA pain. The tidemark (junction between calcified and non-calcified articular cartilage) forms a barrier to diffusion and mass transport of molecules from within the synovial cavity into subchondral bone. In OA, this barrier is disrupted, initially by the penetration of vascular channels from subchondral bone spaces into the non-calcified cartilage, and later through fissuring or cleavage of the articular surface leading to microscopic or macroscopic chondral defects. Osteochondral defects are further associated with bone marrow lesions and articular pain. Far from being a passive, degenerative disease, OA is associated with increased metabolic activity and growth in subchondral bone. Sensory nerve growth from subchondral bone leads to innervation of vascular channels within the non-calcified cartilage, and so a tissue that is normally not innervated might become a source of OA pain. BMLs and increased osteoclast activity are also observed in rheumatoid arthritis, especially in late stage disease. Novel pharmacological interventions might complement joint replacement surgery as a means of reducing arthritis pain originating in subchondral bone.