D-lactic acidosis has been reported in patients after a variety of gastrointestinal surgeries, particularly jejunoileal bypass. An insufficient length of small intestine to metabolize ingested carbohydrates leads to an abnormal carbohydrate load in the colon. These carbohydrates are metabolized by colonic anaerobes (especially Lactobacillus species) into the dextrorotary isomer of lactate. Unlike its levorotary counterpart, D-lactate has neurotoxic effects and patients suffering from a significant D-lactate burden may suffer encephalopathic symptoms. These symptoms are usually mild and self-limiting in patients with normal renal function. We present here a case of D-lactic acidosis in a patient with end-stage renal disease who developed recurrent and life-threatening respiratory failure due to severe D-lactic acid encephalopathy. To our knowledge, no previously reported case has been sufficiently severe to necessitate endotracheal intubation and mechanical ventilation. An array of treatments including hemodialysis effected a prompt reversal of sensorium to baseline. We describe the potential treatments for D-lactic acidosis, which can be viewed as a paradigm of substrate, catalyst and pathologic product and review reports of their relative efficacy.