Posterior reversible encephalopathy syndrome (PRES) is increasingly diagnosed in the emergency department, and medical and surgical intensive care units. PRES is characterized by acute onset of neurologic symptoms in the setting of blood pressure fluctuations, eclampsia, autoimmune disease, transplantation, renal failure, or exposure to immunosuppressive or cytotoxic drugs, triggers known to admit patients to the intensive care unit (ICU). Although the exact pathophysiology remains unknown, there is growing consensus that PRES results from endothelial dysfunction. Because of the heterogeneous nature of the disorder, it is probable that different mechanisms of endothelial injury are etiologically important in different clinical situations. The presence of bilateral vasogenic edema on brain imaging, particularly in parieto-occipital regions, is of great diagnostic utility but PRES remains a clinical diagnosis. Although largely reversible, PRES can result in irreversible neurologic injury and even death. The range of clinical and radiographic manifestations of the syndrome is probably broader than previously thought, and it is imperative that clinicians become familiar with the full spectrum of the disorder, as prompt recognition and elimination of an inciting factor improve outcome. PRES may be the most frequent toxic-metabolic encephalopathy seen in the ICU.