In this article, we review and discuss the pathophysiology of brain ischemia, focusing on requirements of cerebral metabolism, biochemical characterization of the energy reserve, and autoradiographic and tomographic methods for in vivo evaluation of cerebral blood flow and metabolism. We propose new therapeutic strategies for the management of the acute phase of stroke, based on diagnostic protocols that include clinical evaluation, noninvasive study of neck and intracranial arteries, brain computed tomography, and single-photon emission computed tomography. The ideal therapeutic trial should combine early thrombolysis and active brain protection against those biochemical mechanisms leading to irreversible neuronal damage.