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ABSTRACT Bone marrow lesions are abnormalities in magnetic resonance images that have been associated with joint pain and osteoarthritis in clinical studies. Increases in the volume of bone marrow lesions have been associated with progression of joint degeneration, leading to the suggestion that bone marrow lesions may be an early indicator of—or even a contributor to—cartilage loss preceding irreversible damage to the joint. Despite evidence that bone marrow lesions play a role in osteoarthritis pathology, very little is known about the natural history of bone marrow lesions and their contribution to joint degeneration. As a result, there are limited data regarding the cell activity within a bone marrow lesion and any associated bone‐cartilage cross‐talk. Animal models provide the best approach for understanding bone marrow lesions at their early, reversible stages. Here, we review the few animal studies of bone marrow lesions. An ideal animal model of a bone marrow lesion occurs in joints large enough to accurately measure bone marrow lesion volume. Additionally, the ideal animal model would facilitate the study of bone‐cartilage cross‐talk by generating the bone marrow lesion immediately adjacent to subchondral bone and would do so without causing direct damage to neighboring soft tissues to isolate the effects of the bone marrow lesion on cartilage loss. Early reports demonstrate the feasibility of such an animal model. Given the irreversible nature of osteoarthritic changes in the joint, factors such as bone marrow lesions that are present early in disease pathogenesis remain an enticing target for new therapeutic approaches. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.