Pufferfish are generally believed to be the second-most poisonous vertebrates in the world, after the golden poison frog. They use tetrodotoxin, a powerful neurotoxin.

Most pufferfish are found in sub-tropical and tropical marine waters (including coral reefs) in the Atlantic, Pacific, and Indian Oceans. Some pufferfish live in brackish and fresh water.

The scientific name refers to the four large teeth, fused into an upper and lower plate, which are used for crushing the shells of crustaceans and mollusks, their natural prey. Even though pufferfish are poisonous, the meat of some species is eaten in Japan (as 河豚, pronounced 'fugu'), Korea (as 복 bok or 복어 bogeo ), and China (as 河豚 hétún). It is prepared by specially trained chefs who know which parts, and how much of them, are safe to eat.

Aside from extant pufferfish, there are also prehistoric pufferfish, like Zignoichthys. Some people also keep pufferfish as pets.