Sublingual immunotherapy (SLIT) was proposed for clinical practice about 20 years ago with the main aim of improving the safety and of avoiding the side effects. More than 30 randomized controlled trials have been published so far, in addition to several post marketing surveys. Thus, the literature provides a solid documentation of the safety profile of this treatment. Concerning the randomized controlled trials, the more frequently reported side effect of SLIT is the oral itching or swelling, followed by gastrointestinal complaints. These side effects are invariantly described as mild and easily managed by temporarily adjusting the dose. Systemic relevant adverse events (asthma, urticaria, angioedema) occur sporadically, with their rate not being different from the placebo groups. Moreover, the safety profile seems not to differ in adults and children. More interestingly, the post marketing surveys consistently showed that the occurrence of all side effects is less than 20% of patients and less than 1 per 1,000 doses, thus being quite insignificant compared to subcutaneous immunotherapy. The most recent surveys showed that the rate of adverse events does not increase in children below the age of 5 years, being traditionally considered as a prudential limit for injection IT. Finally, it seems that the occurrence of some adverse events, at variance with injection route, does not depend strictly on the dose of allergen administered.