The ever increasing use of magnetic resonance imaging in clinical practice has led to the recognition of a new entity, bone marrow lesions (BMLs). These lesions are characterized by excessive water signals in the marrow space and have emerged as a central component of many different diseases affecting the musculoskeletal system. BMLs have in particular been associated with a wide variety of inflammatory and non-inflammatory rheumatologic conditions and are not only considered significant sources of pain, but also linked to the worsening of patient prognosis in many disease states. In this review, we summarize the current knowledge on BMLs with an emphasis on the clinical and histological features of this entity in inflammatory and non-inflammatory disease and provide a unifying hypothesis based on the appearance with various imaging technologies. We also try to pair this hypothesis with the apparent beneficial effects of various treatment regimens, mainly within the group of bone antiresorptive drugs (calcitonin, bisphosphonates) on symptoms associated with BMLs.