Subcutaneous immunotherapy (SCIT) is effective and safe when properly prescribed and administered. However, a certain risk of severe side effects exists, even when the reaction is managed correctly. These potential adverse effects stimulated the search for new administration routes (nasal, bronchial, oral, sublingual), which were expected to be safer. Not all of these alternative routes provided an improved benefit–safety profile compared with SCIT. The sublingual route (SLIT) seemed to be a good candidate for the clinical practice because of its satisfactory safety profile and is now considered an acceptable alternative to SCIT in adults and children.