Recent achievements in researching botulinum neurotoxin actions′ mechanism are as follows. (1) Electrophysiology experiments demonstrate the decrease of Ca²⁺ sensitivity in the transmitter release system is responsible to the synaptic block induced by BoNTs. Directly intracellular introducing of BoNTs shows BoNTs have no intracellularly cholinergic specificity and inhibit secretion from all types of cells. (2) Binding experiments indicate the binding of BoNTs includes an initial low-affinity step and a subsequent high-affinity step. The low-affinity receptors might be gangliosides, while the high-affinity receptor might be synaptotagmin, a synaptic vesicle membrane protein. (3) The intoxication of BoNTs is more appropriately described by a four-step process: binding to the preferential receptors, internalizing by the process of receptor-mediated endocytosis, membrane translocation and escaping endosomes by an acidification process, as well as selectively cleaving the proteins involved in exocytosis as an enzyme. The carboxyterminus and the aminoterminus of the heavy chain as well as the light chain play important roles in tissue targeting, internalization, and intracellular target modification respectively. The internalized light chain cleaves the proteins involved in the fusion of synaptic vesicles so that the exocytosis as well as the transmitter releases are inhibited.