Emergency physicians regularly attend to patients presenting with acute psychosis; of these cases 20% are found to have a purely medical etiology. The acutely psychotic patient's loss of contact with reality increases the potential for violence. Their bizarre disruptive behavior creates a level of anxiety among ED staff members seldom seen with major trauma. Although patients with psychiatric complaints are often concurrent alcohol or drug abusers, it is a dangerous assumption that this strange behavior can be solely attributed to substance abuse. Failure to address the possibility that a medical emergency may have precipitated a change in behavior endangers the patient by passing his or her care to a physician (the psychiatrist) and facility (the psychiatric hospital), which may be inadequately equipped to handle the medical illness that precipitated the psychosis. Transfer of care offers the illusion to the psychiatric team that the patient has received what is commonly referred to as “medical clearance.” The possibility of a medical cause for a psychotic presentation might not then be readdressed for some time, delaying diagnostic and therapeutic interventions. These deceptively acute patients require that the emergency physician ensure their safety within the department, diffuse any confrontation, and attempt to determine a medical cause. Appropriate stabilization and treatment follow as a matter of course. Finally, a safe and appropriate disposition for the patient must be provided. This article discusses the types of psychosis and a differential diagnosis for them, and provides an approach to initial management.