The lactic acidosis hypothesis of cerebral ischemia has relied on a single finding to support its main postulate: pre-ischemic hyperglycemia-aggravated ischemic brain damage. Although this finding is by no means the proof that the lactic acidosis hypothesis desperately needs, the premise of the hypothesis has been employed in hospitals around the world. A better understanding of some of the processes involved in elevating blood glucose levels pre-ischemia and their influence on the ischemic brain is now available. This understanding offers a unique opportunity to re-examine old dogmas and propose new ideas, in the form of an alternative hypothesis to explain ‘the glucose paradox of cerebral ischemia’.