Mediastinal masses in the newborn represent a wide variety of congenital and neoplastic lesions, which can present interesting diagnostic and therapeutic challenges. However, despite the heterogeneous makeup of this group of lesions, an accurate preoperative diagnosis can usually be established on the basis of the location of the mass. Although many of these mediastinal masses may grow in utero and appear quite prominent on prenatal ultrasound, watchful waiting is recommended unless the fetus is severely compromised. Indications for prenatal intervention may include compression from the mass on the esophagus that may lead to polyhydramnios; compression on the mediastinal lymphatics, veins, and heart that may lead to hydrops and heart failure; and compression on the lungs that may lead to pulmonary hypoplasia and respiratory failure after birth.