The dramatic increase in allergic disease is now an enormous healthcare burden in many countries. Because most current treatment strategies are directed only at controlling the symptoms of these common, disabling and potentially life threatening conditions, there is now a pressing need to define strategies which can directly target, reverse or even prevent the underlying immunological processes. Recent technological advances have provided a better understanding of underlying disease processes and offered new potential therapeutic targets. Optimal treatment strategies permanently modify underlying inflammatory allergic immune responses (immunotherapy) with long-term alleviation of symptoms and minimal side effects. Although these processes are still not completely understood, methods of modifying allergen recognition by the immune system have already been successful. Here, we review recent developments and future directions in allergen immunotherapy and adjunctive therapies. Specifically, we address the molecular mechanisms of allergen immunotherapy, newer routes, and new techniques including allergen modification, allergen gene vaccination, CpG immunostimulation and peptide immunotherapy. Other non-allergen specific molecular targets (including receptor, cytokine and IgE targets) that may complement specific immunotherapy are also discussed. Ideally these methods will eventually be replaced by strategies targeting the prevention of allergic responses (immunoprophylaxis).