Allergy vaccination (AV) consists of injecting increasing amounts of offending allergens into sensitive patients with the intention of reducing their level of sensitivity to allergens. This form of therapy was first used over one hundred years ago and until recently had not changed in principle. The vaccines themselves are now far better characterised and standardised, according to new regulatory requirements. The therapy is believed to exert its effects by a combination of means: by the induction of blocking antibodies; a switch from a T helper (Th)2 to a more Th1 allergen-specific immune response; and induction of anergy, probably via the development of allergen-specific regulatory T cells. New allergen forms and formulations are being designed with these targets in mind. Allergoids (allergens chemically modified to reduce allergenicity, but to retain immunogenicity) are becoming employed more frequently. More modern depot forms, such as those containing tyrosine or calcium phosphate, are replacing aqueous extracts and older depot adjuvants such as alum. T cell-reactive peptides and recombinant allergens or their muteins are also being studied as replacements for whole extracts and have shown some potential. Immunomodulators, such as monophosphoryl lipid A (MPL), designed with defined targets in mind are now included in some vaccines and help to accelerate the process. All these measures have led to a reduction in the need for the traditional long injection schedules. The authors are very familiar in particular with the background to the use of MPL as an adjuvant. They have been personally involved in the development of this approach, which has led to a product being available for use on a regular basis in some European countries. Hence, this work is reported in considerable detail. Other similar immunomodulators, such as CpG motifs, are in development, while new targets, such as the Notch protein/receptor interaction, are exciting new developments that may eventually bear fruit. The excellent safety profile of the sublingual route of administration of allergy vaccines could lead to the wider use of AV, and locally active immunomodulators could make AV a therapy of choice for many more patients than at present.