Acute psychosis is characterized by symptoms such as hallucinations and delusions, although catatonia and disorganized thought may also be present. Distinguishing an underlying cause from a primary disorder is a focus of initial evaluation. Secondary causes of psychosis include some mood disorders such as major depressive disorder, exposure to certain substances, and many medical conditions. Legal medications and illicit substances can cause hallucinations and delusions. Medical conditions include central nervous system infection or primary neurologic causes such as dementia or traumatic brain injury. When found, secondary causes should be treated. Psychosis associated with substance use, such as cannabis or methamphetamine, will usually resolve within 30 days of abstinence from the substance. Primary psychosis is typically treated with a second-generation antipsychotic medication, and the specific choice of medication depends on the patient’s symptoms, desired outcomes, and adverse effect profile of the medication. Antipsychotic medications should be used with caution in older adults and patients with dementia-related psychosis due to the associated risk of mortality. Clozapine is an effective antipsychotic medication with severe adverse effects that requires close monitoring.