Mpox (formerly monkeypox) is a DNA virus of the Orthopoxvirus genus, similar to smallpox. Although mpox was endemic to the Democratic Republic of the Congo and parts of Africa, increasing numbers of cases were reported worldwide in 2022. More than 30,000 cases have been reported in the United States, and worldwide 98% of cases are found in men who have sex with men. Transmission is primarily through contact with skin lesions. The rash of mpox is often vesiculopustular and may be localized to the anogenital region or distributed on the face, trunk, limbs, palms, and soles. Two vaccines are available for pre- or postexposure prophylaxis. Jynneos (smallpox and mpox vaccine, live, nonreplicating) is a live, attenuated vaccine that is safe for patients who are immunocompromised. ACAM2000 (smallpox [vaccinia] vaccine, live) is a live vaccinia virus vaccine that should be given only to immunocompetent, nonpregnant people and should be avoided in those with skin conditions such as atopic dermatitis. For most people infected with mpox, the disease is mild and self-limiting. Antiviral treatments such as tecovirimat, cidofovir, or brincidofovir may be considered for use in individuals who have or are at high risk of severe disease. Possible complications of mpox include anogenital pain, bacterial superinfections of skin lesions, dehydration secondary to oral lesions, encephalitis, keratitis, and respiratory distress. To date, 38 deaths have been reported in the United States.