|“||Don't worry. Most creatures I meet can't get it up for iron. It's a common monster problem.||”|
— Dean to a Phoenix
Creatures that Iron affects
- Acheri - Contact with iron will force an Acheri to dissolve and temporarily retreat. 
- Demons- Touching iron will burn a demon, they also can't cross iron, much like salt. Their weakness to iron is so strong, that even Azazel, one of most powerful demons, who was immune to many other demon weaknesses, was still affected by iron (most likely because it formed a Devil's trap). The only known demons immune to iron are Samhain and Alastair (it is unknown if iron is effective on Lilith, Azazel, or the Knights of Hell like Abaddon).
- Fairies - All fairies are weakened by iron, although powerful ones like Leprechauns can shrug it off. 
- Ghosts - Shooting or stabbing a ghost with iron will temporarily make the ghost disappear. Ghosts also can't cross iron, much like demons. Sam and Dean considered cold iron to be the best way to repel vengeful spirits. If a person possessed by a spirit touches something made of pure iron the spirit will be forced out of the human.
- Hellhounds- They can be killed using iron, as demonstrated in the episode "Abandon All Hope..." in which Ellen and Jo sacrifice themselves to destroy the attacking hellhounds by detonating a propane bomb filled with iron nails and rock salt. 
- Leshi - The only way to kill a Leshi, is to cut off its head with an iron axe. 
- Phoenix - Iron burned the Phoenix's skin, and it couldn't touch Iron, or if imprisoned by it, escape. 
- Shtriga - Consecrated Iron bullets are the only known thing that can kill a Shtriga. 
- 'Edward Trenton's Species' - Although his kind still surrounded by mystery, at least, one of them could be killed by a steel knife coated by silver.
- Witches - Although Iron doesn't hurt witches, it blocks their powers, as Dean used it to restrain James Frampton and he was unable to escape from them or astral project.  Olivette was also bound by Iron when Crowley captured her for his mother Rowena and was left powerless.