Osteoarthritis (OA) is considered a multifactorial disease whose development and progression may include several structural abnormalities aside from cartilage destruction. Bone marrow lesions (BMLs) have been reported to be associated with OA pathology, and several studies have advocated its close connection to the severity of joint structural alterations and pain, the main OA clinical manifestation. Hence, BMLs may not only affect subchondral bone and its neuronal and vascular structures but also negatively influence the adjacent tissues. Here, we analyze the pathophysiology and natural history of OA-associated BMLs and their potential relevance to the radiographic progression and severity of the disease. The notion that BMLs may be a precursor to additional articular abnormalities, can be a potential risk factor for development of OA, and may serve as an additional diagnostic tool and a therapeutic target are further discussed.