Cerebral edema is commonly associated with cerebral pathology, and the clinical manifestation is largely related to the underlying lesioned tissue. Brain edema usually amplifies the dysfunction of the lesioned tissue and the burden of cerebral edema correlates with increased morbidity and mortality across diseases. Our modern-day approach to the medical management of cerebral edema has largely revolved around, an increasingly artificial distinction between cytotoxic and vasogenic cerebral edema. These nontargeted interventions such as hyperosmolar agents and sedation have been the mainstay in clinical practice and offer noneloquent solutions to a dire problem. Our current understanding of the underlying molecular mechanisms driving cerebral edema is becoming much more advanced, with differences being identified across diseases and populations. As our understanding of the underlying molecular mechanisms in neuronal injury continues to expand, so too is the list of targeted therapies in the pipeline. Here we present a brief review of the molecular mechanisms driving cerebral edema and a current overview of our understanding of the molecular targets being investigated.