Introduction: Botulinum toxin (BT) is used in many medical specialties to treat muscle hyperactivity, exocrine gland hyperactivity and pain disorders. BT drugs consist of botulinum neurotoxin (BNT), complexing proteins (CP) and excipients. Antibodies can be formed against BNT and CP. When they are formed against BNT (BTAB) they can block BT's therapeutic efficacy thus producing antibody induced therapy failure (ABTF).Areas covered: BT applied and BTAB are in a functional balance within the body. ABTF is rare, but influences the treatment algorithms of BT therapy considerably. ABTF risk factors include BT doses given, interinjection intervals, booster injections and immunological quality of the BT drug. Testing for BTAB and interpretation of ABTF is complicated. As management of ABTF is frustrating, prevention of ABTF is of major importance. Improved antigenicity of new BT drugs may improve treatment algorithms of BT therapy, substandard antigenicity may very likely be their end.Expert commentary: Concern about ABTF has influenced the treatment algorithms of BT therapy considerably. Better understanding of ABTF may improve them and, thus, the outcome of BT therapy. New BT drugs may have further improved antigenicity, especially when their CP are removed. They may, however, fail because of antigenicity problems.