PURPOSE: Subchondral bone marrow lesions (BMLs) are present in a wide range of pathologies with different prognoses. Thus, a careful diagnosis is mandatory to address them with the proper treatment. The aim of this review was to examine BMLs aetiology and their relationship with biomechanical and biological factors, to identify BMLs and help clinicians to properly recognize and treat each of these common alterations. DISCUSSION: Each pathological pattern is determined by different aetiologic factors, which may act alone or synergically in determining the BML. These factors include major or minor trauma, bone tissue alterations, altered joint load distribution, coagulopathies, and hormonal alterations. This narrative review encompasses these patterns and factors providing a nosographic and etiopathogenetic framework for subchondral BMLs in the knee. CONCLUSION: While the field is still heterogeneous in the definition of the nosographic framework of BMLs, there is a trend with the convergence towards a common terminology, which could help to shed more light on the complex and varied field of BMLs. Future studies should focus on better understanding the etiopathogenetic mechanisms, which can concur with the development of BML from one side, and, on the other hand, may represent targets for future treatments to address BMLs and preserve or restore the osteochondral unit. LEVEL OF EVIDENCE: Expert Opinion, Level V.