The Reversible Splenial Lesion Syndrome represents a distinct clinicoradiological syndrome, associated with several disorders, including infection, high altitude cerebral edema, antiepileptic drug withdrawal, and severe metabolic disturbances (hypoglycemia and hypernatremia). Clinical presentation is nonspecific, most frequently as an encephalopathy or encephalitis. Outcome is favorable in most patients unless there is a severe underlying disorder. Magnetic resonance imaging findings are restricted to the splenium and consist of a nonenhancing oval lesion, hyperintense on T2-weighted images, including FLAIR. Findings on diffusion-weighted imaging are consistent with cytotoxic edema except for high-altitude cerebral edema, where vasogenic edema is present. Resolution after weeks or months is the rule.