| The Caves
| Ball of Bandages|
|Defeating Mom for the first time.|
•Pestilence will float around the room, leaving a trail of poison.
•In addition to the trail of poison, he will fire explosive projectiles at Isaac which too, leave poison.
•Pestilence can also summon up to four Chargers or Spitties
•Pestilence is now headless and will shoot the explosive projectiles randomly rather than directly at Isaac.
•Instead of Chargers or Spitties, Pestilence will summon Attack Flies.
White: Will leave a trail of white creep, which slows the player down; and now shoots 6 bullets away from him instead of explosive shots. He now spawns Spiders instead of flies in Phase 2.
- Pestilence, in some interpretations, is one of the Four Horsemen of the Apocalypse.
- Conquest is often replaced by Pestilence in popular culture. Originally, Conquest is the first of the horsemen depicted in the Bible (Rev 6:2).
- Pestilence means a virulent or fatal disease epidemic.
- The entirety of Pestilence's offense deals with poison and bugs that are associated with rot.