Posterior Reversible Encephalopathy Syndrome (PRES) is a neurotoxic condition with a distinctive brain imaging pattern, often linked to various clinical conditions such as preeclampsia, allogeneic bone marrow transplantation, solid organ transplantation, autoimmune diseases, and high-dose cancer chemotherapy. The exact mechanism of vasogenic edema in PRES remains unclear, with two main theories: 1) severe hypertension leading to failed autoregulation, hyperperfusion, and endothelial injury; and 2) vasoconstriction and hypoperfusion causing brain ischemia and subsequent edema. While the hypertension/hyperperfusion theory is popular, recent evidence suggests that systemic immune challenges and T-cell/endothelial activation may be more relevant, leading to vasoconstriction and hypoperfusion. Autoregulation of cerebral blood flow is crucial, with the brain's vascular system maintaining stable blood flow despite fluctuations in blood pressure. However, when blood pressure exceeds autoregulatory limits, it can lead to hypoperfusion, ischemia, and vasogenic edema. Studies show that hypertension is common in PRES, but not always reaching autoregulatory limits. Additionally, brain edema in PRES does not correlate with the severity of hypertension, suggesting that other factors, such as systemic toxicity, may be more significant. PRES can occur in normotensive patients and those with mild hypertension, indicating that systemic processes, rather than hypertension alone, are key. Conditions associated with PRES, such as preeclampsia, transplantation, infection, and autoimmune diseases, share common features like immune activation, endothelial injury, and inflammatory cytokine release. These processes lead to vasoconstriction, hypoperfusion, and subsequent vasogenic edema. Evidence supports that systemic toxicity, rather than hypertension, is the primary driver of PRES. Hypoperfusion and vasoconstriction are central to the pathophysiology, with vascular dysfunction and endothelial activation playing key roles. Imaging studies show features consistent with hypoperfusion, such as watershed distribution and reduced cerebral perfusion. The role of hypertension in PRES is complex, with it potentially acting as a modulator rather than the primary cause. Magnesium levels and other factors may also influence the condition. Overall, the pathophysiology of PRES is multifactorial, involving systemic immune responses, endothelial dysfunction, and vascular changes. Further research is needed to clarify the exact mechanisms and improve treatment strategies for PRES.Posterior Reversible Encephalopathy Syndrome (PRES) is a neurotoxic condition with a distinctive brain imaging pattern, often linked to various clinical conditions such as preeclampsia, allogeneic bone marrow transplantation, solid organ transplantation, autoimmune diseases, and high-dose cancer chemotherapy. The exact mechanism of vasogenic edema in PRES remains unclear, with two main theories: 1) severe hypertension leading to failed autoregulation, hyperperfusion, and endothelial injury; and 2) vasoconstriction and hypoperfusion causing brain ischemia and subsequent edema. While the hypertension/hyperperfusion theory is popular, recent evidence suggests that systemic immune challenges and T-cell/endothelial activation may be more relevant, leading to vasoconstriction and hypoperfusion. Autoregulation of cerebral blood flow is crucial, with the brain's vascular system maintaining stable blood flow despite fluctuations in blood pressure. However, when blood pressure exceeds autoregulatory limits, it can lead to hypoperfusion, ischemia, and vasogenic edema. Studies show that hypertension is common in PRES, but not always reaching autoregulatory limits. Additionally, brain edema in PRES does not correlate with the severity of hypertension, suggesting that other factors, such as systemic toxicity, may be more significant. PRES can occur in normotensive patients and those with mild hypertension, indicating that systemic processes, rather than hypertension alone, are key. Conditions associated with PRES, such as preeclampsia, transplantation, infection, and autoimmune diseases, share common features like immune activation, endothelial injury, and inflammatory cytokine release. These processes lead to vasoconstriction, hypoperfusion, and subsequent vasogenic edema. Evidence supports that systemic toxicity, rather than hypertension, is the primary driver of PRES. Hypoperfusion and vasoconstriction are central to the pathophysiology, with vascular dysfunction and endothelial activation playing key roles. Imaging studies show features consistent with hypoperfusion, such as watershed distribution and reduced cerebral perfusion. The role of hypertension in PRES is complex, with it potentially acting as a modulator rather than the primary cause. Magnesium levels and other factors may also influence the condition. Overall, the pathophysiology of PRES is multifactorial, involving systemic immune responses, endothelial dysfunction, and vascular changes. Further research is needed to clarify the exact mechanisms and improve treatment strategies for PRES.