Pollen allergy affects at least 10% of the global population, and up to one-third of the affected individuals displaying hay fever symptoms will later develop allergic asthma. The efficacy of allergen-specific immunotherapy (SIT) in seasonal allergic rhinitis has been confirmed in many clinical studies using grass, ragweed, and birch pollen extracts. SIT prevents the onset of new sensitizations to different allergens, and reduces the development of asthma in patients with allergic rhinitis caused by inhaled allergens, including pollen. Several rational approaches are being developed to improve the efficacy of SIT by reducing immunoglobulin (Ig)E-mediated adverse reactions. The use of chemically modified, recombinant or genetically engineered allergens is being explored, in addition to the investigation of novel adjuvants and alternative routes of administration. The first clinical trials using recombinant allergens provided encouraging results, suggesting that allergen extracts can be successfully substituted by molecule-based formulations. These new formulations, for use in the routine management of pollen allergies, should become available in the near future.