Botulinum toxins are metalloproteases that act inside nerve terminals and block neurotransmitter release through their cleavage of components of the exocytosis machinery. These toxins are used to treat human diseases that are characterized by hyperfunction of cholinergic terminals. Recently, evidence has accumulated that gangliosides and synaptic vesicle proteins cooperate to mediate toxin binding to the presynaptic terminal. The differential distribution of synaptic vesicle protein receptors, gangliosides and toxin substrates in distinct neuronal populations opens up the possibility of using different serotypes of botulinum toxins for the treatment of central nervous system diseases caused by altered activity of selected neuronal populations