Allergy/immunology specialists in the US prescribing allergy immunotherapy (AIT) have placed a heavy value on practical experience and anecdotal evidence rather than research-based evidence. With the extensive research on AIT conducted in the last few decades, the time has come to better implement evidencebased medicine (EBM) for AIT. The goal of this review was to critically assess EBM for debated concepts in US AIT practice for respiratory allergies in the context and quality of today's regulatory standards. Debated topics reviewed were the efficacy and safety of AIT in various subgroups (e.g., polyallergic patients, older patients, patients with asthma, pregnant women), diagnosis topics (e.g., skin prick test vs allergen-specific serum IgE, factors affecting skin prick tests, use of nasal or conjunctival allergen challenges, and telemedicine for diagnosis), and dosing topics (e.g., optimal dosing for subcutaneous immunotherapy and sublingual immunotherapy tablets, US liquid allergen extract history, duration of treatment, biomarkers of efficacy). In addition, EBM for patient-centered AIT issues (e.g., adherence, use of practice guidelines, pharmacoeconomics) and the approach to implementation of AIT EBM in future clinical practice was also addressed. The EBM for each concept was briefly summarized, and when possible, a practical, concise recommendation was given.