Posterior reversible encephalopathy syndrome (PRES) is a rare clinical-radiological entity characterised by seizures, severe headache, mental status instability and visual disturbances. Hypertension is typically present. We report a case of a 13-year old boy with Burkitt lymphoma/leukaemia, who presented with posterior leukoencephalopathy 24 hours after intrathecal methotrexate (MTX) infusion. The child presented with headache, seizures, elevated blood pressure and gradual deterioration of his neurological status. Midazolam, dexamethazone and furosemide were initiated leading to reduction of cerebral oedema and clinical improvement. A thorough literature review is discussed in this report. Pathophysiology of leukoencephalopathy remains unclear. It develops within 5-14 days after intrathecal MTX and resolves within a week usually without permanent neurological sequelae. Broad use of MRI has led to an increasing number of identified cases of PRES. Treatment approach is mainly to manage the underlying cause of PRES. Prognosis is generally benign; however delayed diagnosis and improper management may result in permanent brain insult.