The classic terminology "osteochondritis dissecans (OCD)" describes a pathologic alteration, centered at the osteochondral junction, involving the subchondral bone and/or its cartilaginous precursor, with risk for lesion instability and disruption of the overlying articular cartilage. Among children and young adults, these sites of osteochondrosis can be a cause of chronic joint pain and are most often found within the knee, the ankle, and the elbow joints. No consensus exists on the precise pathophysiology underlying the development and progression of these lesions, which likely varies slightly among lesions at different anatomic locations as the result of region-specific differences in tissue quality, vascular perfusion, and biomechanical forces. While our current understanding of OCD lesions is largely derived from lesions involving the femoral condyles, important location-dependent differences exist. The current Part I article of this two-part series will review key definitions and pathophysiologic principles shared among OCD lesions, highlighting the distinction between lesions that occur in skeletally immature and mature individuals. This will be followed by a brief section on the imaging approach and rationale for imaging work-up. Finally, an evidence-based literature review will address location-specific pathophysiology, imaging considerations, findings of lesion instability, and treatment selection considerations, focusing on lesions that involve the knee joint: medial femoral condyle, lateral femoral condyle, and patellar-femoral trochlear joint. A separate article (Part II of this series) will be devoted to lesions that involve the ankle (talar dome) and the elbow (capitellum and humeral trochlea) joints.