Allergen-specific immunotherapy is aimed at modifying the natural history of allergy by inducing tolerance to the causative allergen. In its traditional, subcutaneous form, immunotherapy has complete evidence of efficacy in allergic asthma. However, subcutaneous immunotherapy (SCIT) has a major flaw in side effects, and especially in possible anaphylactic reactions, and this prompted the search for safer ways of administration of allergen extracts. Sublingual immunotherapy (SLIT) has met such need while maintaining a clinical efficacy comparable to SCIT. In fact, the safety profile, as outlined by a systematic revision of the available literature, was substantially free from serious systemic reactions. A number of meta-analyses clearly showed that SLIT is effective in allergic rhinitis by significantly reducing the clinical symptoms and the use of anti-allergic drugs, while the efficacy in allergic asthma is still debated, with some meta-analyses showing clear effectiveness but other giving contrasting results. Besides the efficacy on symptoms, the preventive activity and the cost-effectiveness are important outcomes of SLIT in asthma. The needs to meet include more data on efficacy in house dust mite asthma, optimal techniques of administration and, as previously done with SCIT, introduction of adjuvants able to enhance the immunologic response and use of recombinant allergens.