The subchondral bone is involved in the pathophysiology of osteoarthritis (OA), both by biochemical and mechanical pathways. Overloaded OA subchondral bone osteoblasts express a pro-angiogenic and pro-inflammatory phenotype which contributes to explain the structural changes (sclerosis and bone marrow lesion) visible in OA subchondral bone. Further, microfractures and conjonctivo-vascular structures constitute exchange routes between bone and the overlying cartilage for mediators produced by osteoblasts. This narrative review describes these physiopathological mechanisms and identifies possible therapeutic targets for pharmacological modalities.