For many years, pharmaceutical therapies for osteoarthritis (OA) have been focused on the degenerating cartilage. However, there is increasing evidence that bone plays an important role in OA as well. The structural and material properties of the subchondral bone are modified, and bone cysts and osteophytes may develop. The mechanisms behind these bone changes are subject of debate, and a better understanding may help in the development of bone-targeting OA therapies.