Botulinum toxin (trade name Botox) inhibits acetylcholine release in neurons and causes botulism, an acute paralytic disease which leads to nerve degeneration and takes a long time to recover. I've read the statement that Botox is the most potent poison we know a few times now and was wondering why exactly it is. All sources I've found only claim that it is, without explanation.
A quick search for a list of LD50 (median lethal dose; half of the people will die with that dosage) gave me 1 ng/kg for Botulinum toxin. This is pretty darn small amount, and in fact the smallest amount within that table.
The biochemical mechanism of BT is pretty well laid out at Wikipedia already. The toxin is likely very potent because (1) it is targeted to neurons; (2) neurons endocytose BT; and (3) the BT light chain's protease activity is able to cleave a wide range of SNARE-complex proteins which effectively disrupt the neurons ability to secrete monoamine neurotransmitters, and peptide hormones. Basically, the neurons are completely inhibited from transmitting nerve impulses.