Despite the consensus that glutamatergic and GABAergic imbalance is likely to be involved in anesthesia or coma, there is little known about molecular mechanisms of action of gaseous anesthetics. The target article by Smythies (1999) is engagingly analytical and insightful, proposing novel and testable hypotheses for the molecular mechanisms of action of anesthetics as well as for processes that may be involved in coma. The most creative and convincing of his hypotheses concerns the crucial role of iron in maintaining neural respiration and energy production as well as its involvement in synaptic plasticity. Smythies' paper is certain to stimulate new ideas and experiments on the molecular mechanisms of anesthesia and coma.