Allergen-specific immunotherapy is the only treatment of allergic diseases that aims at modifying the underlying immune mechanism. Current protocols are long and at risk of anaphylactic reactions. The main aim of current research is decreasing the risk of side effects and increasing efficacy, in particular targeting reduction of treatment duration. Since the advent of molecular biology, extracts can be replaced by recombinant hypo-allergens, peptides, or fusion proteins. In addition, different routes of administration are being pursued as well as the addition of new adjuvants that are targeted at skewing the immune system away from a Th2 to a more Th1 or regulatory T cell phenotype. In this review, we summarize the recent advances in this field focusing on the allergen modifications and new adjuvants.