Brain swelling is an urgent clinical problem that frequently accompanies ischemic stroke, brain hemorrhage, and traumatic brain injury; it increases morbidity and mortality associated with them. It occurs due to failure of membrane transporters and leakage of the blood–brain barrier (BBB), resulting in combination of cytotoxic, ionic, and vasogenic edema. Currently, decompressive craniectomy and osmotherapy are the mainstays of management, but these therapies do not halt the underlying molecular cascade leading to brain swelling. Recent advances in the molecular underpinnings of cerebral edema have opened up possibilities of newer targeted therapeutic options. Here the authors outline the current approach for rapid diagnosis and intervention to reduce mortality and morbidity associated with brain swelling.