Many medications and toxins may induce central nervous system (CNS) depression. Even when the intention is to induce CNS depression, other nervous system adverse effects may occur, such as with anesthetics. Pain medications produce characteristic CNS toxicities. Sedative hypnotics may induce altered mentation among systemic toxicities. Stimulants may mimic coma when discontinued abruptly. Acute and chronic carbon monoxide poisoning can lead to altered mental status and prolonged cognitive difficulties. Some medications and environmental toxins can mimic brain death. High clinical suspicion and early recognition of these effects is vital to treatment, most of which is supportive.