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Infantile hemangiomas are the most common vascular tumor of infancy. Treatment of infantile hemangiomas was revolutionized when propranolol, a nonselective β-blocker, was reported to be effective therapy. In this review, we highlight the lessons learned using propranolol to treat infantile hemangiomas. We also describe the ongoing effort to understand the mechanism of action of propranolol.Although the pathogenesis of infantile hemangiomas is not fully understood, maternal hypoxic stress and embolization of placental tissue are suggested to be critical components in their development. The mechanism of action of propranolol remains unclear, however various molecular mechanisms are detailed in this review. Propranolol treatment remains a well tolerated therapy, with low risk of adverse events or long-term neurocognitive effects. Dosing recommendations and optimal treatment duration vary among studies, and should be altered in patients with certain medical conditions such as Posterior fossa anomalies, Hemangioma, Arterial lesions, Cardiac abnormalities/coarctation of the aorta, Eye anomalies (PHACE) syndrome.Propranolol is a well tolerated and effective treatment for infantile hemangiomas. The efficacy of propranolol for infantile hemangiomas is clear, however questions pertaining to mechanism of action, pretreatment risk stratification, and optimal dosing remain unanswered. The guidelines for managing infantile hemangiomas with propranolol will continue to adapt as research catches up to clinical experience.