Congenital cytomegalovirus (CMV) is the most common viral infection, affecting nearly 40,000 infants each year in the United States. Of seronegative women, 1-4% will acquire a primary infection during pregnancy, and the majority of these women will be asymptomatic. Prior maternal exposure to CMV does not preclude neonatal infection. The purpose of this document is to review diagnosis of primary maternal CMV infection, diagnosis of fetal CMV infection, and whether antenatal therapy is warranted. We recommend the following: (1) that women with a diagnosis of primary CMV infection in pregnancy be advised that the risk of congenital infection is 30-50%, on average, and that the severity of infection varies widely (Best Practice); (2) for women suspected of having primary CMV infection in pregnancy, we recommend that diagnosis should be either by IgG seroconversion or with positive CMV IgM, positive IgG, and low IgG avidity (grade 1B); (3) amniocentesis is the best option as a prenatal diagnostic tool to detect fetal congenital CMV infection, performed >21 weeks of gestation and >6 weeks from maternal infection (grade 1C); (4) we do not recommend routine screening of all pregnant women for evidence of primary CMV infection at this time (grade 1B); and (5) we do not recommend antenatal treatment with ganciclovir or valacyclovir; and we recommend that any antenatal therapy, either with antivirals or CMV hyperimmune globulin, should only be offered as part of a research protocol (Best Practice).