Silithus forms the southwestern corner of Kalimdor. It can only be reached by traveling to the northwestern corner of Un'Goro Crater, where a wide path extends out of the crater and into Silithus.

Silithus is one of the bug-infested sections of southern Kalimdor. This area houses a section of the once great Aqiri empire, known as Ahn'Qiraj. It is currently uninhabited, but the central temple is sealed off by the night elves, who attempted to prevent an infestation from breaking out. Judging by the ruins in the area, as well as the massive Silithid colonies, they were unsuccessful in their attempt. The Cenarion Circle maintains a constant presence in Silithus at Cenarion Hold. From here, they monitor the Silithids, whom some believe to be a force so powerful and threatening that the Alliance and Horde must ally to combat it. In addition to the Cenarion Druids, a second, more ominous presence has recently made itself known in Silithus. The bronze dragonflight, Nozdormu's brood, has returned to the desert for the first time in ten thousand years.

Silithus has been fleshed out as a major quest hub with episodic storylines that extend into its depths and past its borders. The redesign of this zone includes a high-end outdoor quest area for solo players, while 5-man groups can tackle outdoor raid bosses. The repeatable quests can lead to epic items as a casual alternative to raid dungeons.

Silithus has for thousands of years held the prison of the Qiraji, trapped behind the Scarab Wall in the aftermath of the War of the Shifting Sands. The Qiraji's servants, the silithids, have since multiplied and spread across southern Kalimdor. Seeing this, the night elves decided to reopen the Gates of Ahn'Qiraj to put an end to the Qiraji threat once and for all.