Congenital heart disease comprises one-third of all major birth defects. Prevalence estimates depend on the definition of the disease and the postnatal period when the disease is diagnosed. The studies with the longest follow-up estimate that 0.9% of infants are afflicted. The cause of these cardiac defects is largely unknown. The effect of embryonic exposure to maternal drugs during cardiogenesis has been widely studied, and the evidence suggests that maternal use of ethanol, anticonvulsants, lithium, and exogeneous female hormones may increase the risk of congenital heart disease. An antiemetic agent containing doxylamine has been implicated in the courts. This review offers an analysis of the epidemiologic evidence of the occurrence of congenital heart disease in relation to maternal drug use during pregnancy. The evidence indicates that the vast majority of heart malformations cannot be attributed to these pharmacologic agents.