Most Puffer species produce a slime coating mucus on their skin, called Tetraodoxin (correct me at any time).. It is this mucus, which is found most concentrated on the inside of the puffer, that is lethal to humans. In some species, it is supposively more lethal than cyanide! Don't EVER lick or bite your puffers! (Please I hope you don't..)
HOWEVER, personal experience and studies have shown that most Puffers in captivity lose the ability to produce Tetraodoxin because their dietary needs change. So whatever they eat in the wild that allows them to produce Tetraodoxin, is not found in home aquariums. (I am assume it to be certain crustacea or shellfish..)