Since its introduction the safety of specific immunotherapy (SIT) was assessed by many well-designed studies. SIT is accepted as an effective treatment of allergic diseases despite the occurrence of side-effects, among which systemic reactions (SRs) are the most dangerous. The reported frequency of SRs after SIT varies among the studies and several factors influence it. Asthma is a particular risk factor for systemic side-effects. Furthermore, SRs occur more often in patients with high allergen sensitivity as determined by skin testing or RAST. Making dosage errors is also considered to be a high risk. It is reported that reactions are more common during rush and clustered induction treatment, whereas a significantly lower incidence of SRs occurred with the use of standardized modified allergen vaccines than with aqueous extracts. On the basis of valuable guidelines, precautions to minimize the risk of SRs from SIT were recommended. Injections should be given or supervised by doctors well-trained in this form of treatment in a clinic where there is the immediate availability of a resuscitative equipment. Consideration should be given to evaluate the patient's conditions and to monitor subjects for a minimum of 30 minutes after the injections. Therefore, if appropriately done, the risk of SIT is negligible.