Malignant cerebral infarction refers to a large-volume ischemic stroke associated with life-threatening space-occupying cerebral edema, which may lead to intracranial hypertension, brain herniation, and subsequent fatal clinical deterioration. It accounts for approximately 10% of all ischemic strokes, with a mortality rate of 80% despite the best medical treatment. Decompressive craniectomy (DC) is a life-saving surgical procedure that involves the removal of a significant portion of the skull and the opening of the dura mater. The goal of DC is to allow for external herniation of the edematous brain, decrease intracranial pressure and brain compression, and increase cerebral blood flow. DC can significantly reduce mortality to 20%. However, survivors often have poor functional outcomes due to the severity of the stroke. Randomized studies have confirmed that DC is effective in patients ≤60 years of age if performed before clinical deterioration occurs, ideally within 48 hours of the onset of the ischemic event. In patients >60 years of age who neurologically deteriorate within 48 hours, surgical decompression can be considered on an individual basis. A decrease in the level of consciousness attributed to brain edema could be the trigger for DC. The expected functional status and quality of life based on preoperative predictions, which would be acceptable to patients and relatives, should be an essential part of the complex decision-making process. The chapter comprehensively reviews the issue of DC in malignant ischemic stroke, both supratentorial and infratentorial. It provides an overview of randomized studies and current guidelines. A detailed description of the technical aspects of decompressive craniectomy, including its complications, treatment alternatives, and cranioplasty, is presented. The parameters influencing the decision-making process regarding indications and clinical outcomes are reviewed.