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Background: Early recognition of duct-dependent congenital heart disease in newborns with duct-dependent pulmonary or systemic blood flow or transposition of the great arteries is critical for early introduction of prostaglandin E1 (PGE1), which allows stabilization of the newborn till cardiac catheterization or surgical intervention. Indications for PGE1, management of newborns with duct-dependent congenital heart disease and interventions in case of side effects of PGE1 are reviewed. Conclusions: It is critical to start with PGE1 infusion as soon as we clinically suspect ductdependent congenital heart disease. With this approach, morbidity and mortality of newborns with congenital heart disease is significantly reduced.