Rapid diagnosis and management of stroke patients is becoming increasingly important with the emergence of new interventional strategies for acute cerebral ischemia. A biochemical surrogate of cerebral ischemia, rapidly detectable in the serum before radiological diagnosis, might have clinical utility in the setting of acute stroke, high-risk cardiovascular procedures, and subarachnoid hemorrhage. Such a marker might also aid in the neurological prognosis of anoxic brain injury. Several serum markers have been evaluated in acute cerebral ischemia. These include neuronal enzymes such as neuron-specific enolase; markers of glial injury and activation, such as protein S100beta; and mediators of inflammation, such as interleukin-6. The clinical and preclinical data supporting the use of these biochemical surrogates of cerebral ischemia are reviewed.