Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke because of large vessel occlusion (LVO), but distal and medium vessel occlusions (DMVOs) remain a gray zone. DMVOs account for a substantial proportion of ischemic strokes and can cause long-term disability or death despite often presenting with only mild to moderate symptoms. Their biologic and anatomic diversity—including small vessel caliber, variable perfusion territories, collateral dependence, and complex access pathways—creates distinct patterns of natural history, treatment responsiveness, and procedural risk compared with proximal LVO.