The brain is considered the most eloquent organ in the human body as its activities impacts on all other systems. Though protected physically (in a bony covering), physiologically through the blood-CSF barrier (from invading organisms and toxins) and hemodynamically through the phenomenon of cerebral autoregulation; the brain is open to insults of various kinds which can critically damage this structure. Intracellular Ca++ accumulation, excessive activation of excitatory amino acid receptors, lipid peroxidation and free radical releaserelated damage are but a few of the pathological processes that occur at the neuronal level leading to damage. The mechanism by which the brain can be provided protection when it is in a compromised state or likely to be compromised is known as cerebral protection. There are various modalities of pharmacologic (use of barbiturates, etomidate, isoflurane, steroids, Ca++, corticosteroids etc) and non-pharmacologic therapies (hypothermia, hyperventilation, induced hypotension, electrophysiologic monitoring, endovascular management etc) available for cerebral protection which finds place in the armamentarium of clinicians managing the critically injured brain. Our knowledge of the functioning of the brain at the molecular level and the various biochemico-pathological processes that are set into motion during critical states continues to evolve. This review article attempts to explain present understanding of the biochemical and pathological processes involved in neuronal damage while also looking at current available therapies (pharmacologic & nonpharmacologic) being utilized in different clinical settings.