Botulinum neurotoxins (BoNTs) are the deadliest poisons known to man. They possess a particular duality, rapidly increasing clinical utility for a wide range of disorders and large concern as a possible weapon of bioterrorism. While great strides have been made in the structural and biochemical understanding of the mechanism of intoxication, the specific molecular details behind BoNT translocation out of endosomes remain elusive. In this study, it was conclusively demonstrated that light chain metalloprotease translocation can only occur in the presence of low pH, as is found in endosomes, and GT1b ganglioside coreceptor, whose role was previously thought to only be in cell surface recognition by the toxin. As stated by the authors, the BoNT receptor-binding domain therefore serves as a 'coincidence receptor' in that pH sensing and conformational change to a translocation competent form must be coupled in some way to receptor binding. Further study using atomic force microscopy also suggested the presence of oligomeric toxin channels that can be inhibited by the natural product toosendanin. This data revises the model of BoNT intoxication and demonstrates a mechanism for the amazing temporal and spatial control possessed by this toxin, which ultimately manifests in its extreme potency.