Infantile hemangioma (IH) is a benign vascular tumor, characterized by a unique sequence of non-linear growth and spontaneous involution. Some hemangiomas require intensive treatment to avoid functional and aesthetic insufficiency. Although β-adrenergic receptor (β-AR) antagonists have been increasingly used as the first-line treatment since 2008, the IH rebound still exists with uncertain mechanism. Here, we report three cases of abrupt IH deteriorations that are mainly related to β2-AR agonist administration. Potential IH proliferation induced by β2-AR agonists, especially from oral or nebulized approaches, should be recognized more widely by healthcare providers. Additionally, it is necessary to carry out large sample studies to analyze the influence of β2-AR agonist administration on the deterioration of IH.