Chagas disease, caused by the parasite Trypanosoma cruzi (T.cruzi), is an underrecognized health concern in the United States (U.S). An estimated 40,000 reproductive-age women living in the U.S. have chronic Chagas disease, and most are not aware of the infection. The risk of congenital transmission of Chagas disease is 1–5%, with an estimated 22–315 congenital infections each year in the U.S. About 10% to 40% of newborn infants with congenital Chagas disease have clinical signs at birth, including low birth weight, low Apgar scores, jaundice, anemia, or thrombocytopenia, but the diagnosis is often overlooked due to lack of unique clinical features. Neonates infected with T.cruzi, even those who are asymptomatic at birth, remain at risk for the long-term and potentially fatal cardiac or gastrointestinal complications of untreated infection. Molecular testing is the most sensitive approach for establishing the diagnosis of congenital Chagas disease in the first 2 months of life. Treatment of congenital Chagas disease is well-tolerated in infants and provides the best chance to decrease progression risk, resulting in a cure in greater than 90% of cases when treated in the first year of life. Routine screening of at-risk women during pregnancy is needed to identify maternal infection and enable early assessment and treatment for congenital transmission of Trypanosoma cruzi in infants.