Botulinum toxin treatment is the most common non-surgical cosmetic treatment. Although there are many available treatments using botulinum toxin, their effects are temporary and repeated injections are required. These frequent injections can trigger an immunological response. In addition, botulinum toxin acts as an antigen in the body; thus, its effect disappears progressively due to this immunological reaction, which may cause treatment failure. Active botulinum toxin consists of a core neurotoxin and complexing proteins, the exact effects of which remain unclear. However, the complexing proteins are closely related to the immune response and the formation of neutralizing antibodies. Since neutralizing antibodies can lead to treatment failure, their formation should be prevented. Furthermore, various methods of detecting neutralizing antibodies have been used to predict treatment failure.