Subcutaneous allergen immunotherapy (SCIT) is a unique treatment option for managing patients with allergic rhinitis, asthma, atopic dermatitis, and stinging insect allergy. Although systemic reactions to allergen injections are rare, near-fatal, and fatal anaphylactic reactions can occur. Patients with asthma are at greatest risk for more severe reactions as are those with previous systemic reactions. Treating allergists should institute best clinical practices to prevent and manage severe systemic reactions to SCIT, including the following: (1) prescreening patients with asthma for recent increases in asthma symptoms, (2) not prescribing SCIT to patients with severe and uncontrolled asthma, (3) instituting clinic protocols to prevent dosing errors, (4) considering modifying allergen doses during peak allergy seasons in patients at high risk, (5) instituting measures that require all patients on SCIT to be observed for at least 30 minutes after injections, and (6) regular training of all clinical staff in the recognition and expeditious treatment of anaphylaxis.