Intraoperative neurophysiologic monitoring (INM) using somatosensory and motor evoked potentials (MEPs) has become popular to reduce neural risk and to improve intraoperative surgical decision making. Intraoperative neurophysiologic monitoring is affected by the choice and management of the anesthetic agents chosen. Because inhalational and intravenous anesthetic agents have effects on neural synaptic and axonal functional activities, the anesthetic effect on any given response will depend on the pathway affected and the mechanism of action of the anesthetic agent (i.e., direct inhibition or indirect effects based on changes in the balance of inhibitory or excitatory inputs). In general, responses that are more highly dependent on synaptic function will have more marked reductions in amplitude and increases in latency as a result of the synaptic effects of inhalational anesthetic agents and similar effects at higher doses of intravenous agents. Hence, recording cortical somatosensory evoked potentials and myogenic MEPs requires critical anesthetic choices for INM. The management of the physiologic milieu is also important as central nervous system blood flow, intracranial pressure, blood rheology, temperature, and arterial carbon dioxide partial pressure produce alterations in the responses consistent with the support of neural functioning. Finally, the management of pharmacologic neuromuscular blockade is critical to myogenic MEP recording in which some blockade may be desirable for surgery but excessive blockade may eliminate responses. A close working relationship of the monitoring team, the anesthesiologist, and the surgeon is key to the successful conduct and interpretation of INM.