Medium vessel occlusions (MeVOs, ie, M2, M3, A2, A3, P2, and P3 segment occlusions) are increasingly recognized as a target for endovascular treatment in acute ischemic stroke. It is important to note that not all MeVOs are equal. Primary MeVOs occur de novo with the underlying mechanisms being very similar to large vessel occlusion strokes. Secondary MeVOs arise from large vessel occlusions through clot migration or fragmentation, either spontaneously or following treatment with intravenous thrombolysis or endovascular treatment. Currently, there are little data on the prevalence, management, and prognosis of acute ischemic stroke due to secondary MeVOs. This type of stroke is, however, likely to become more relevant in the future as indications for endovascular treatment continue to broaden. In this article, we describe different types of secondary MeVOs, imaging findings associated with them, challenges related to the diagnosis of secondary MeVOs, and their potential implications for treatment strategies and clinical outcomes.