Severe ischemic stroke with progressive edema development is frequently life-threatening and associated with a poor prognosis due to limited expandability within the cranial cavity. This chapter describes the relevant aspects of supra- and infratentorial space-occupying strokes with particular emphasis on the role of decompressive surgery. Large ischemic infarction of the middle cerebral artery (MCA) territory can lead to a clinical syndrome called malignant MCA stroke. Cranial computed tomography (CT) is still the most widely used radiological modality to diagnose and monitor malignant MCA infarction. The only specific treatment option for this type of stroke with a solid base of evidence and major impact on the clinical course to date is decompressive surgery, that is, hemicraniectomy. Swelling of a large space-occupying cerebellar infarct appears within a few days from symptom onset and can lead to compression of the brainstem and midbrain or cause a hydrocephalus.