The Punisher generally stays out of most high-level superhuman conflict, but he has his moments where his Knight Templar nature gets him to go charging off to kill some dangerous people he really shouldn't have been tangling with, like The Incredible Hulk (both the Savage and Joe Fixit versions), Norman Osborn, and Anti-Venom, to name a few.
- Since Frank is a known badass with a body count nearly as high as The Joker, criminals waste no time in throwing their lives away by trying to attack him. Frank, who is inevitably heavily restrained, adds a few more bodies to the count before the guards show up. In The Punisher: The End, the prison authorities at Sing Sing solved the problem by throwing him in solitary confinement before he "killed every inmate we got," to quote one of the guards. It worked, too... until the world blew up.
- When Frank walks in on Anti-Venom busting a Mexican crime syndicate in New Ways to Live, they team up until he realizes Anti-Venom is his old adversary Eddie Brock. Castle promptly shoots Anti-Venom — who was in the process of thanking him — point-blank in the face with a shotgun, and when the last surviving thug takes the ex-drug addict Anti-Venom had been using as an informant hostage, Frank coldly states, "That's not a girl... it's a junkie" and takes aim, causing Anti-Venom to pull his head back together, severely pissed off, and smash Frank through a wall. Frank reluctantly agrees to a truce but spends the rest of the series trying to catch Eddie with his symbiote retracted, rebuking Eddie when he points out that they're very similar, and making no secret of his intent to kill Eddie the moment he lets his guard down.
- In a crossover with Wolverine written by Garth Ennis, Punisher repeatedly abuses Wolverine, including shooting him in the crotch with a shotgun and crushing him under a steamroller. Even though, as he can see, Wolverine keeps getting back up unhurt after each attack. Fortunately, Wolverine never decides to seriously retaliate, though he does swear a grudge on Castle for everything he did to him. Though in Wolverine #186, Wolverine did win a fistfight with Punisher and then mocked him for having a bag full of magazines depicting skimpily-clad muscular guys. And then Wolverine's Bastard Bastard son Daken killed Castle.
- In The Incredible Hulk #395, Punisher decides to go after "Mr. Fixit" during a trip to Vegas. Thing is, Mr. Fixit is an alter-ego of the Hulk, and so Punisher's attack doesn't exactly work out how he expected. He riddles Fixit with bullets, to no avail, even when shooting at the eyes, and then throws a grenade at him, which is smacked back at Frank by one of Hulk's allies — and only doesn't blow himself up because he had the good fortune to run into "The Professor" (Hulk with Banner's personality dominant), so he caught the grenade and let it blow up inside his clenched fist. Then, when Frank attacked him with a knife, Hulk tapped him on the head with one finger and knocked him out cold.
- In Marvel Zombies vs. Army of Darkness #2, he ignores the zombie plague to continue business as usual, alienating or killing off his potential allies before ultimately being devoured by a bunch of superhuman zombies.
- In Runaways #26, he makes the mistake of threatening the Runaways at gunpoint for their criminal relations. Pint-Sized Powerhouse Molly promptly punches him in the gut so hard that it takes all of Frank's willpower not to collapse on the spot, and he is effectively taken out of action and is comically left standing in one place trying to move but unable to because of the pain.
- He once tried to go up against the Spider-Man villain Doctor Octopus, in revenge for being ambushed earlier and to stop his plan of poisoning a large number of people with a slow poison and holding their lives for ransom. Ock doesn't even look at Frank while his arms disarm and pin him down before force-feeding him the above-mentioned poison, and Castle almost died, and survived only due to Spider-Man.
- The Kingpin is another Spider-Man villain who tore Frank a new one. Frank has gotten into fights with Kingpin more than once, but it keeps ending the same way with Kingpin nearly killing Frank. Except in an arcade game, where while Kingpin is a very tough boss gameplay-wise, Frank still beat him.
- Nicky Cavellla from The Punisher MAX. He wanted to eliminate the Punisher and thought he could do it by making him clumsy. To do that, Nick dug up the Punisher's family's remains, pissed on them while recording himself doing so, and sent the video to the local news. His plan worked, and Frank stopped being as methodical as he normally is, but with the trade-off that Frank went into such an Unstoppable Rage that he killed several important figures in Cavella's criminal family in one day. The remaining family ditched Cavella and Frank shot him in the stomach.
- Because of his disdain for superheroes, who are "too soft on crime", the Punisher has often assaulted far more powerful superheroes. Whether he gets away with it or not tends to depend on if he's being written by Garth Ennis.
- On the "gotten away with it" side, the Punisher once blew off the face and balls of Wolverine with a shotgun, and then ran him over with a steamroller. He also once shot Anti-Venom before trying to kill Anti-Venom's Morality Chain, Jenna Cole. Admittedly, Anti-Venom proceeded to punch Frank through a wall, but considering Anti-Venom's sporadic wrestling with cannibalistic urges, it could have gone a lot worse for Frank. Also, in another comic, Frank and Wolverine met, and Wolverine decided to take revenge for the above. Cue No-Holds-Barred Beatdown.
- On the "didn't get away with it" side... In Marvel Knights, Frank once tried to pick a fight with Ulik the Rock Troll, a monster and regular foe of The Mighty Thor. The only reason Frank survived was that Daredevil ran off and found the magical whatsit that Ulik was after whilst Ulik was kicking Frank around like a football. In The Superior Foes of Spider-Man, the Shocker blows Frank away with all the ease of swatting a fly, thanks to his sonic blasters being more than Frank's body armor can hope to handle. In Runaways #26, he makes the mistake of threatening the Runaways at gunpoint for their criminal relations. Pint-Sized Powerhouse Molly promptly punches him in the gut so hard that it takes all of Frank's willpower not to collapse on the spot, and he is effectively taken out of action. And then there's the the time he tries to assassinate Norman Osborn... who is, at the time, not only still his Green Goblin self, but also the head of an evil version of SHIELD AND the leader of the Dark Avengers who have provided him with The Sentry as a bodyguard. The result is that the assassination attempt fails miserably due to Sentry interfering, and then the only reason he isn't captured is that Frank set off a bomb elsewhere at which Sentry flew off to protect people from the explosion. Osborn sends Daken (Wolverine's Ax-Crazy son with the same power set) after the Punisher, and he ends up unceremoniously cut into pieces and dumped down a sewer.note