* AnticlimaxBoss: Bokrug is, with difference, the easiest Ancient One in the game. His Doom Track is relatively forgiving, and if you're diligent killing monsters and closing gates you can get rid of the four Beings of Ib before he awakens, which leaves him with very little means to screw you over in a significant manner. Additionally, one of his Sinister Plots makes him turn around and [[ScrewThisImOuttaHere go back to sleep]], ending the game in ([[AntiClimax an admittedly anticlimactic]]) victory for the Investigators.
** Yig has been statistically one of the easiest to defeat Ancient Ones, even between different versions of him.
** [[UnskilledButStrong Ithaqua]]. He doesn't have too many checks you have to pass, and the battle is basically a straight-up physical brawl. If you use Call Ancient One when you're armed to the teeth, you have a shot at taking him out.
** Azathoth, despite his RocksFallEveryoneDies combat, is still fairly easy to beat, as he takes a long time to wake up, has a very minor game-affecting ability, and sealing gates tends to be the most common way to win. He's often recommended as a [[WarmUpBoss beginner boss]] because he's so simple and people can focus on learning basic strategies.
* DemonicSpiders: The Hound of Tindalos; it's one of the few monsters that can attack you in any location, can move anywhere on the board, and if playing a low sanity character (poor Monterey Jack), it's almost impossible to fight as it will just nuke your brain instantly.
** Plain ol' ghosts from the main game also count. They're immobile, not to mention ''immune to physical attack'' and have hefty penalties on Will, Fight, and Sneak checks. In the wrong place against an ill-equipped character, they are a formidable roadblock.
** Dholes. Resistance to both stats, lethal damage, high stats and toughness...the only thing keeping you sane is that it moves normally, meaning you can generally walk around it.
* GameBreaker: Despite the game's punishing difficulty, some investigators can really stick it to the Ancient Ones:
** Mandy Thompson is undeniably the strongest investigator in the original game and arguably this with expansions included. She starts with 4 clue tokens, which lets her seal a gate earlier than usual, and more importantly, her ability allows any one investigator per turn to reroll failed dice in a skill check. Any chance of being screwed over by bad dice rolls, whether in sealing a gate, killing a monster, or passing a risky event, can be remedied once every turn. She's only somewhat mitigated by her rather high-stakes personal story and low stats.
* ThatOneBoss: Great Cthulhu himself. His cultists affect your sanity like most other monsters. Everyone permanently loses a point of maximum health and sanity with him in play. In the final battle, he regenerates a doom token after every attack.
** Atlach-Nacha is the most feared Ancient One in the game, and for good reason; sealing gates, the main method of defeating the Great Old Ones, barely inconveniences him at all. He is also extremely difficult to defeat once he awakens (though not impossible like Azathoth).