Anesthetics are widely used in experiments investigating neurotoxicity and neuroprotection; however, these agents are known to interfere with the outcome of these experiments. The purpose of this overview is to review these effects and suggest methods for minimizing unintended consequences on experimental outcomes. Information on the neuroprotective and neurotoxic effects of isoflurane, dexmedetomidine, propofol, ketamine, barbiturates, halothane, xenon, carbon dioxide, and nitrous oxide is summarized. The pertinent cell signaling pathways of these agents are discussed. Methods of humane animal euthanasia without anesthetics are considered. Most anesthetics alter the processes of neuronal survival and death. When designing survival surgeries, sham controls subjected to anesthesia but not the surgical intervention should be compared with controls subjected to neither anesthesia nor surgery. Additional controls could include using an anesthetic with a different mechanism of action from the primary anesthetic used. Because the effects of anesthetics lessen with time after surgery, survival surgeries should include later time points until at least 7 d after the procedure. Humane methods of animal euthanasia that do not require anesthetics exist and should be used whenever appropriate.