The emergence of the monkeypox outbreak in early 2022 has posed a new global health threat. As of July 8, 2022, 9,069 laboratory-confirmed cases have been reported, and most of them are from non-endemic countries. The monkeypox virus is an enveloped double-stranded DNA virus, and preliminary genetic data suggest that the 2022 monkeypox virus belongs to the West African clade. In the current outbreak, human-to-human transmission has been the primary transmission mode. Although direct skin-to-skin contact with lesions during sexual activities can spread the virus, it remains unclear whether monkeypox can spread through sexual contact, specifically through contaminated body fluids. The typical presentation of monkeypox includes prodromal symptoms, followed by a rash that usually begins within 1–3 days of symptom onset, and the skin lesions can last for 2–4 weeks and then gradually resolve. However, the monkeypox outbreak in 2022 may exhibit atypical features. A definite diagnosis of monkeypox virus infection requires nucleic acid amplification testing via the polymerase chain reaction method. Supportive care is essential, and antiviral therapy is not considered for all affected patients, but recommended for those at highrisk for severe diseases. The mitigation of monkeypox outbreaks include enhanced case detection, case isolation, contact tracing, and post-exposure vaccination. In conclusion, the current monkeypox outbreak is a new threat during the COVID-19 pandemic. Clinicians should be aware of this new situation, which presents a different scenario from those of prior outbreaks. Global health systems should develop effective strategies to mitigate the spread of monkeypox.