The discovery in the 1970s that hyperglycemia accompanying cerebral ischemia adversely affected survival led to a significant research effort on the biochemical, histological, and clinical consequences of cerebral acidosis. In this article, we review the methods used currently to measure cerebral pH and discuss the means the cell has to control its pH environment. We then discuss the influence of both normoglycemic and hyperglycemic cerebral ischemia on pH and conversely the effect of acidosis on cerebral blood flow (CBF), glycolysis, mitochondrial function, the blood-brain barrier, cellular volume control, the formation of cerebral edema, and the histological damage resulting from ischemia. We conclude with a discussion of how acidosis could worsen the derangement in calcium homeostasis known to occur as a consequence of ischemia, and review methods now available to counteract cerebral acidosis.