Botulinum neurotoxin (BoNT) is a bacterial toxin that causes paralysis. Recent models have suggested that BoNT recognizes and enters nerve endings by interacting with protein receptors and gangliosides, which are glycosphingolipid components of the cell membrane that modulate cell signaling. Recent structures provide insight into how BoNT interacts with these cell surface components and open the door for the development of inhibitors against this neurotoxin.