Botulinum toxin type A is a high molecular weight protein complex containing active neurotoxin and complexing proteins, the latter of which, it is believed, protect the neurotoxin when in the gastrointestinal tract, and may facilitate its absorption. Comparisons of conventional botulinum toxin type A drugs that include complexing proteins with the complexing protein-free formulation of Xeomin^® strongly suggest that complexing proteins do not affect diffusion of the active neurotoxin. Studies of Xeomin have also shown that complexing proteins do not enhance product stability in storage. However, complexing proteins may stimulate antibody development against botulinum toxin type A. Numerous observational studies have been published showing that some patients receiving conventional botulinum toxin may develop neutralizing antibodies, leading to antibody-induced therapy failure. Studies have shown that Xeomin is not associated with the development of neutralizing antibodies in animal models or in patients. In conclusion, complexing proteins do not contribute to the stability of botulinum toxin type A drugs and do not contribute to their therapeutic effects, but may be associated with a secondary nonresponse due to the development of neutralizing antibodies.