Silver
In the Supernatural 'verse, many creatures are vulnerable to weapons made of silver.
Silver bullets are used to dispatch Madison the werewolf in 2.17 Heart, the shapeshifters in 1.06 Skin and 4.05 Monster Movie. Another shapeshifter is killed after being stabbed with a silver letter opener in 2.12 Nightshifter. The Alpha Shapeshifter appears to be immune to Silver.
Silver blades were also used to destroy the djinn in 2.20 What Is and What Should Never Be and in 6.01 Exile On Main St., the wraith in 5.11 Sam, Interrupted, and are mentioned as a weapon against lamias in 6.04 Weekend At Bobby's.
For the Djinn the silver had to be dipped in lamb's blood, and for the lamia, it needed to be blessed. Silver stakes are also used to 'kill' zombies in 2.04 Children Shouldn't Play With Dead Things and 4.07 It's The Great Pumpkin, Sam Winchester; in the former, silver bullets weakened the zombie but did not kill it.
The Skinwalker Lucky in 6.08 All Dogs Go To Heaven is restrained by Sam and Dean using silver chains. The other Skinwalkers are killed by the Winchesters with silver bullets. Lucky is shot, but survives.
Silver is also used as a test by some hunters to see if they are dealing with a human. When Dean returns from Hell 4.01 Lazarus Rising Dean cuts himself with a silver blade to try and demonstrate his humanity as does Sam on his return from Lucifer's Cage6.01 Exile On Main St.
In 4.19 Jump The Shark, Dean replaces the diner cutlery with silver utensils to test whether Adam Milligan is human. He does not react to the silver, but is not human. He is in fact a ghoul, a being unaffected by silver, pretending to be Adam.
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