Since May 2022, more than 6,900 cases of monkeypox virus infection have been reported in 52 countries. The World Health Organization is planning to rename the virus and its clades to reduce stigma. As of July 5, 2022, 556 cases have been reported in 33 U.S. states and the District of Columbia. The initial cases were travel-associated; however, person-to-person transmission is now occurring domestically. Close, sustained skin-to-skin contact, including during sexual activity, appears to be the primary mode of transmission. The risk of widespread community transmission remains low; however, rapid identification of monkeypox virus infection and isolation of affected individuals is critical to prevent further transmission. Most but not all cases have occurred in males; some infections have started with anogenital lesions and can be mistaken for common sexually transmitted infections. To facilitate rapid, accurate diagnosis of monkeypox virus infection, obstetrician–gynecologists (ob-gyns) in the United States should ask about recent travel history and new ulcers or lesions and perform a thorough visual inspection of skin and mucosal sites (oral, genital, perianal area) in patients presenting with new rash. Obstetrician–gynecologists should become familiar with the appearance of monkeypox lesions and know whom to call to report a suspected case, how and when to test for monkeypox virus, and how to counsel patients. In the event of a suspected case, ob-gyns should follow infection-control guidelines to prevent transmission and make recommendations to prevent further community spread. This article outlines the diagnosis, prevention, and treatment of monkeypox virus infection, monkeypox virus infection during pregnancy, and implications for practicing ob-gyns in the United States.