Infantile hemangiomas (IHs) are the most common tumors in infancy. Their typical natural history is characterized by an early rapid growth in the first months of life and by a slow spontaneous involution in the first years of life. Even though spontaneous regression of IHs could suggest therapeutic abstention, systemic treatment is the therapy of choice in many patients in which these situations occur: 1) rapid growth of IHs; 2) location of IHs in aesthetically critic areas; 3) recurrent hemorrhages, ulcerations or infections of IHs; 3) IHs interfering with important physiological functions (breathing, feeding, vision, hearing, etc.); 4) large or multicentric IHs that can cause heart failure. Since 2008, systemic administration of propranolol, an old non‑selective β‑blocker, was found, serendipitously, to improve the treatment of IHs replacing older and more dangerous therapies like oral steroids, vincristine, interferon‑alpha or vascular lasers. At present, oral propranolol has dramatically changed the approach of IHs because its efficacy is almost 100% and its action is rapid, without important side effects. The formal approval by FDA and EMA has been obtained in Spring 2014.