Purpose The objective of this clinical review is to provide an overview of antiviral therapies for monkeypox treatment and summarize the role of vaccines in monkeypox prevention. Summary The human monkeypox virus is a double-stranded DNA virus of the Orthopoxvirus genus of the Poxviridae family. The estimated case fatality rate for monkeypox ranges between 0% and 11%. The first human monkeypox infection was reportedly due to an unidentified animal reservoir. Per the Centers for Disease Control and Prevention, isolation and infection control procedures should be followed in the care of those infected with monkeypox virus. Monkeypox virus infection symptoms include rash, fever, chills, headache, muscle aches, backache, and fatigue that may progress to exhaustion. Severe complications such as encephalitis, pneumonia, and retropharyngeal abscess could appear in immunocompromised or critically ill patients. There are currently no specific Food and Drug Administration (FDA)–approved therapies for monkeypox. As with most viral infections, supportive care is the backbone of monkeypox clinical management. However, therapies effective for smallpox, such as cidofovir, brincidofovir, and tecovirimat, have previously been reported to be effective in the management of monkeypox. Pre- and postexposure prophylaxis to prevent monkeypox transmission are recommended in the US for those at high risk for disease transmission. Conclusion There are no FDA-approved treatments for monkeypox infection. Surveillance and detection of monkeypox among high-risk populations should be implemented to help understand the epidemiology of this disease.