Allergen immunotherapy has proved to be an efficacious option for many suffering from severe allergies (Oktemer T, Ame J Rhinol Allergy, 30:4–7, 2016). However, as this treatment modality involves exposing the patient to specific allergens, it is not without risk. This chapter will cover topics related to adverse reactions during immunotherapy including risk factors, pathophysiology, varying types and severities, treatment options, prevention, and future considerations.