Monkeypox is an uncommon viral zoonosis caused by the monkeypox virus (MPV), a member of the genus Orthopoxvirus. MPV is a large, complex, double-stranded DNA virus of the chordopoxvirus family. MPV is endemic in central and western Africa and is a classic zoonosis acquired through contact with infected rodents and squirrels. Observational studies of human monkeypox in central and western Africa have revealed that MPV infection has an incubation period of 10-14 days and a period of infectivity during the first week of rash. MPV enters the body through skin abrasions, the upper respiratory tract mucosa, or by ingestion. During primary viremia, the virus migrates to regional lymph nodes and then disseminates throughout the body. Vaccination with vaccinia virus (smallpox vaccine) is highly protective (around 85%) against MPV infection. Post-exposure smallpox vaccination is indicated for persons who are at high risk of MPV infection, including those investigating animal or human monkeypox cases, health care workers caring for infected patients, and laboratory workers who handle specimens that may contain MPV.