Microdialysis, an in vivo technique that permits collection and analysis of small molecular weight substances from the interstitial space, was developed more than 30 years ago and introduced into the clinical neurosciences in the 1990s. Today cerebral microdialysis is an established, commercially available clinical tool that is focused primarily on markers of cerebral energy metabolism (glucose, lactate, and pyruvate) and cell damage (glycerol), and neurotransmitters (glutamate). Although the brain comprises only 2% of body weight, it consumes 20% of total body energy. Consequently, the ability to monitor cerebral metabolism can provide significant insights during clinical care. Measurements of lactate, pyruvate, and glucose give information about the comparative contributions of aerobic and anaerobic metabolisms to brain energy. The lactate/pyruvate ratio reflects cytoplasmic redox state and thus provides information about tissue oxygenation. An elevated lactate pyruvate ratio (>40) frequently is interpreted as a sign of cerebral hypoxia or ischemia. However, several other factors may contribute to an elevated LPR. This article reviews potential non-hypoxic/ischemic causes of an increased LPR.