The New Plague is the Forsaken's altered version of the powerful Plague of Undeath that led to the creation of the Undead Scourge. The Plague of Undeath had the effect of transforming normal humans into mindless undead in the service of the tyrannical Lich King. Some members of the Forsaken, including their queen Sylvanas Windrunner, were once pawns of the Lich King, but were later freed. The Forsaken's aim is to create a new plague that would annihilate the Scourge itself, and perhaps later their living enemies as well — and raise them to replenish and expand their own numbers.
The Royal Apothecary Society, the alchemical experts of the Forsaken, have been working on various ways to use various parts from creatures living in their sphere of control as well as agriculture grown in the Tirisfal Glades and the Hillsbrad Foothills to create powerful toxins. The nearest brush with success yet seen involved pumpkins from the Solliden Farmstead in Tirisfal. When tested on a Scarlet Crusader held captive in the Brill Inn, it brought about transformation into a ghoul, only to cause true death seconds later.
The use of the New Plague on humans has thus far been only partially successful. While it kills the victim, it doesn't bring the human back after death as a new Forsaken. Other problems remaining include distribution; the Royal Apothecary Society is searching for a way to effectively spread their new plague, so that no living thing remains on the entire planet...leaving all of Azeroth as one big plagueland, ruled by the Forsaken. Sylvanas' initial plan is to wipe out her immediate enemies — the Scourge and then the Alliance, and raise them again to her cause.
Castillian was responsible for delivering spores which helped lead to the finalization of the New Plague.
Infiltrator Marksen seems to know what the Forsaken are up to.
Quests that refer to the new plague in World of Warcraft
In Wrath of the Lich KingThis section concerns content exclusive to Wrath of the Lich King.
The towns of New Agamand and (to a lesser extent) Vengeance Landing in the Howling Fjord and the town of Venomspite in the Dragonblight are the Forsaken's major centers for production of the "New Plague" in Northrend. After several failures in Howling Fjord, the apothecaries of New Agamand send a sample of the perfected plague, known as the "Forsaken Blight", to Venomspite. The Forsaken Blight, combined with a reactive agent, is powerful enough to turn its victims (or at least the undead ones) into shapeless piles of goo. In the quests  and  , Horde players are sent to find said reactive agent (the ectoplasmic residue from the ghosts of Arthas' troops on the Forgotten Shore) and a vessel to contain them (tears of green dragons from the Emerald Dragonshrine). Before delivering the plague to Doctor Sintar Malefious in Agmar's Hammer, the player must drive a Forsaken "blight spreader" catapult from Venomspite to an area of the Carrion Fields outside of Wintergarde Keep, right in the shadow of Naxxramas, to test this new blight on the Scourge (  ). It appears that the forces of the Scarlet Onslaught are immune to this plague, as indicated in the failed test against an Onslaught Prisoner in  . Amusingly, Alliance players also accidentally create the Blight in the quest  , which entails a drunken gnome alchemist sending the player to give an 'antidote' to a vrykul prisoner, which causes him to dissolve into a pile of goo. Upon completion, the quest giver says, "Huh? Well that sucks! Darn, I made thingsh worsh. In fact, I think I perfected their plague for them ...hic!"
The Forsaken Blight's most despicable use occurred during the Battle of Angrathar the Wrathgate. After Dranosh Saurfang was slain by the Lich King while he and Bolvar Fordragon confronted him, Grand Apothecary Putress arrived on the bluff overlooking the battlefield with several blight spreader catapults. Serving the dreadlord Varimathras, who had launched a coup against the Dark Lady and taken control of the Undercity for the Legion, Putress launched the Blight against both the Scourge and the combined Alliance-Horde forces. The attack resulted in the status of Highlord Fordragon becoming unknown, the near-total destruction of the combined army, and even weakened the Lich King, who retreated back into Icecrown Citadel.
The Forsaken attack is considered by the Alliance to be outright treachery on the part of the Horde, and the coup by Varimathras gave King Varian Wrynn an opening to purge the Horde from Lordaeron and retake the city for the Alliance. King Varian leads Alliance forces in a to avenge Bolvar and retake Lordaeron, while the Horde launches to reclaim it from Varimathras.
In CataclysmThis section concerns content exclusive to Cataclysm.
The Horde banned any further use of the Forsaken Blight after the Wrathgate, but Sylvanas had disregarded those orders on two occasions - by using it against the town of Southshore in Hillsbrad Foothills, and intending to do so during the invasion of Gilneas.
Although the Horde did ban it, they gave some apothecaries a weaker version of the blight, which wouldn't be so destructive. It proves to be literally rather explosive when adventurers test it out on murlocs on Fenris Isle.