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A two-vessel umbilical cord (or single umbilical artery) is a perinatal finding that may be detected in infants with congenital or chromosomal abnormalities. Its presence has been associated with an increased risk of genitourinary defects. The urologic anomalies that typically are associated with a two-vessel cord often are minor and self-limiting. These defects usually can be detected perinatally in routine prenatal screening ultrasonographic examinations. The neonatal physical examination, an additional postnatal ultrasonography, and possibly a voiding cystourethrogram will be sufficient to complete the screening for genitourinary abnormalities in children with a single umbilical artery. Infants with two-vessel umbilical cords do not require additional screening for genitourinary defects, unless the imaging or amniocentesis detects a genitourinary abnormality. This review details the history of two-vessel cords and the associated genitourinary anomalies.