Allergic diseases affect millions of adults and children in the United States. Allergen immunotherapy has been a treatment option for diseases such as allergic rhinitis, allergic asthma, and venom allergy for the last 100 years. In the last 25 years, alternative approaches to traditional subcutaneous immunotherapy have been developed. The purpose of these new therapies is two-fold: to improve safety and to improve the efficacy of allergen immunotherapy. Aluminum hydroxide has been used as an adjuvant to standard immunotherapy, but due to concerns about side effects, its use has been decreasing. The modification of allergens into allergoids has been an effective therapy in Europe, but at this time no preparations are available for use in the United States. Toll-like receptors have demonstrated mixed results with early trials in the United States, showing promise with the use of a TLR4 agonist, while a TLR9 agonist had disappointing results. Early studies with the use of virus-like particles with and without allergens have shown additional promise, and further trials are currently underway. These novel approaches may improve the immunologic response and often the clinical outcomes for the management of allergic diseases.