Specific immunotherapy (SIT) is accepted as an effective treatment of allergic diseases when high quality extracts are used. However, this form of treatment can cause untoward reactions among which systemic reactions are the most severe. Although life-threatening reactions are rare and deaths exceptionally reported, SIT should be prescribed by allergists to patients with well defined characteristics, and administered with care by (or under the close supervision of) physicians trained to deal rapidly with the reactions. Reactions with standardised extracts occur mostly during the dose increase phase but they can be prevented using adapted schedules and premedication. During maintenance injections or when vial batches are changed, standardised extracts of known shelf-life usually result in a low rate of systemic reactions. Patients with asthma are more prone to develop systemic reactions, and allergens should not be administered to patients with a forced expiratory volume in 1 second (FEV1) under 70% of predicted or in those who have unstable or symptomatic asthma. Systemic reactions may be observed with all allergens and allergenic preparations although it appears that high molecular weight extracts may be safer.