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If a character has an Achilles Heel -- and especially if they have a Weaksauce Weakness -- inevitably an opponent comes along who is basically made of or otherwise works solely in the medium of Weaksauce. Examples abound, especially in DC Comics. This trope is essentially the ultra-specific, ultra-literalist version of Good Hurts Evil or No Man of Woman Born. Less commonly, a character with no existing vulnerability ends up against a character who introduces a unique weakness of theirs.
For obvious reasons, this is primarily a Comic Book Trope.
Closely related to Kryptonite Is Everywhere. Counterpart to the Kung Fu-Proof Mook. Combine both to create a That One Boss or worse. Contrast This Looks Like a Job For Aquaman, which occurs when a situtation is tailored to avoid a hero's Weaksauce Weakness and utilize their lame power of heart. If the hero manages to defeat this character anyway, it's a form of Scissors Cuts Rock.
- Superman, of course, has met several iterations of the Trope Namer, a villain called the Kryptonite Man, who is Exactly What It Says on the Tin. Metallo and, currently, Reactron also have their primary power as being walking Kryptonite delivery systems, a kind of combination of this trope and Weaponized Weakness.
- Also Kenny Braverman, aka "Conduit" a cyborg powered by kryptonite radiation who's innate power was kryptonite blasts. And for a double whammy, he knew that Clark was Superman leading to the "Death Of Clark Kent" story arc.
- In JLA-Avengers, two Marvel villains (Radioactive Man and Solarr) become this, Lex Luthor having told them about Superman's twin weaknesses of Green Kryptonite and red solar radiation.
- This is both played straight and inverted in Supreme, where Ethan Crane is given his powers by exposure to Supremium but proves weak to it when later faced with the Supremium Man. It was eventually seen that Darius Dax, caught in a time loop, became both the Supremium Man and the original chunk of Supremium, giving Supreme his powers, making him weak, and becoming his greatest enemy, all at the same time.
- During Blackest Night, Dove became this for Black Lanterns.
- The Golden Age Green Lantern was vulnerable to wood, and fought the plant-matter swamp zombie Solomon Grundy, who was immune to his ring. The Silver Age version's weakness to yellow was countered by Sinestro and his yellow power ring, and, more directly, Goldface. Now that the rings' weakness is fear, we have the embodiment of fear, Parallax. Green Arrow also once fought Green Lanterns by painting himself yellow.
- The original Venom was Spider-Man's worst enemy because he had all his powers, wouldn't trigger his Spider Sense, and knew he was Peter Parker. If the symbiote didn't have a few weaknesses of it's own it would have been unbeatable.
- The second type of this trope is the basis of original Venom Eddie Brock's new identity Anti-Venom, whose primary power is to destroy the Venom symbiote. However, Brock also has more general "purification" powers that remove any foreign or artificial enhancements from others. In essence, he's a type 2 Man of Kryptonite for everyone.
- The black suit that eventually became Venom had two weaknesses: fire and sonic attacks. Wouldn't you know it, the short time he had the suit was the only time Spider-Man encountered Humbug, a villain whose power was sonic attacks.
- Nemesis Kid, a Legion of Super-Heroes villain, consciously adapts whatever power he needed to defeat a single foe. If he guesses wrong, he's screwed. He ended up having his neck snapped by a vengeful Queen Projectra, having adapted immunity to her illusion powers, and she used the martial arts training her husband (the aptly named Karate Kid) had given her over the course of their marriage to kill him with her bare hands.
- Marvel Comics demon Nightmare fears one being above all others: the monster Gulgol, who never sleeps and is therefore utterly beyond Nightmare's dream-manipulation powers.
- The Martian Manhunter, who is vulnerable to fire, had the Human Flame as an adversary.
- The Speed-Force-powered Flash's enemy the Turtle was eventually given the power to dampen kinetic energy...in other words, he became a walking anti-Speed Force.
- Pinocchio Vampire Slayer, where the main character's nose alone is the instrument of vampire destruction.
- Anyone could eaisly have been one of these for the second generation green lanterns, due to the fact his weakness was the color yellow, and everyone knew it. Makes you wonder how they managed to stop crime/help the universe etc.
- Jesus Christ Vampire Hunter. Speaks for itself, really.
- This was the drawback of the spell Jonathan used in the Buffy the Vampire Slayer episode "Superstar;" it made him a literal Mary Sue, but also loosed a demon whose mere presence weakened him physically and mentally.
- Ironically, in Smallville, Lana became this for Clark, because writers needed her to leave. For some reason nobody tried to ask for her help with rough Kryptonians later in the show.
- All That gives us Superdude who has the worst weakness ever: extreme lactose intolerance. He can't even touch dairy products without going into shock. Naturally, his villains include Yo-Girl (a feisty chick whose body is a yogurt cup), Butter Boy, and his arch-nemesis the Milkman.