Hemangiomas are the most common benign neoplasm in the neonatal period. While most small hemangiomas involute spontaneously, up to 20% may grow to a massive size and never completely involute. Massive hemangiomas are also frequently associated with life-threatening complications, such as airway obstruction, platelet trapping (Kasabach-Merritt syndrome), and high-output heart failure. The use of interferon alfa-2a for the treatment of massive hemangiomas not responsive to traditional therapy has recently been reported. We present the successful use of interferon alfa-2a in a series of five patients with massive hemangiomas complicated by airway compromise, congestive heart failure, need for tracheotomy, Kasabach-Merritt syndrome, and failure to thrive, despite traditional therapy.