Subcutaneous immunotherapy is a well-documented treatment of allergic rhinitis and asthma. The major limitation is the risk of anaphylactic side effects. The documentation of clinical efficacy is based on crude allergenic extracts sometimes containing varying amounts of individual allergens including allergens to which the patient may not be sensitized. The introduction of recombinant allergens offer a possibility to use well-defined molecules with consistent pharmaceutical quality defined in mass units. The proof-of-concept of the clinical efficacy of recombinant allergens is based on two studies published as full articles. One study applied a mixture of five Phleum pratense major allergens in a maximum dose of 40 μg protein. The clinical efficacy showed a significant efficacy with about 40% reduction in disease severity. The second study compared a commercial birch extract with both recombinant Bet v 1 and purified Bet v 1 in dosages of 15 μg allergen. The clinical effect was around 60% additional efficacy. Systemic side effects occurred more frequently with grass allergens. A third study used hypoallergenic fragments and a trimer of Bet v 1. The study did not show efficacy and a rather high frequency of systemic side effects. The advantages of using recombinant allergens for immunotherapy are obvious but more large-scale clinical studies are needed before the overall value in terms of efficacy and safety can be determined.