Alpha-gal syndrome (AGS) is an emerging allergic disease caused by an immunoglobulin E (IgE) response to galactose-α-1,3-galactose (alpha-gal), a sugar found in mammalian meat. The initial IgE sensitization follows a bite from the (lone star) tick in the United States, although other tick species can also cause the disease. AGS presents with delayed symptoms, primarily gastrointestinal or allergic reactions like urticaria or anaphylaxis, hours after mammalian meat consumption. The nonspecificity of the symptoms can delay the diagnosis of AGS for years. Diagnosis relies on clinical evaluation and detection of alpha-gal-specific IgE in blood. As the lone star tick's range is expanding beyond the southern United States, AGS is gaining recognition in other regions. However, many healthcare providers remain unaware of the condition, leading to misdiagnosis. Infectious diseases physicians who frequently evaluate patients with tick exposure must be familiar with AGS, including tick identification, bite prevention, and knowledge of the alpha-gal-containing vaccines.