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Until recently, she was believed dead. Her experiments led to the creation of the Twilight Dragonflight, through which she planned to rule Azeroth. Her plans never came to fruition, and she was killed during the destruction of her own creation, the twilight dragon Dargonax. However, recent events have revealed that she was reanimated by the power of the Old Gods.
Sintharia was once the prime consort of Neltharion, who later came to be known as Deathwing. She gave birth to some of Deathwing's most despicable children including Nefarian and his sister, Onyxia. After Neltharion's madness overtook him and the rest of the black dragonflight, the newly disfigured Deathwing attempted to mate with his consorts, causing Sintharia a great deal of pain and leaving behind scars and marks that would continue to burn for (at least) the rest of her natural life. Sintharia was the only mate known to have survived.
Approximately five hundred years prior to the opening of the Dark Portal, Sintharia attempted to bring down the Kirin Tor with a curse that left the wizards unable to use their magic. Her scheme was foiled in part by Korialstrasz, consort to Alexstrasza, and when Sintharia was defeated, most believed her to be dead. She survived, however, and forsook her mate and children, taking on the guise of Lady Sinestra, a name she came to use as a dragon as well.
Though the Black Dragonflight is in the process of dying out, that isn't stopping Deathwing from trying to keep it alive. Sinestra's children, Nefarian and Onyxia, have continued their plan of domination even in their father's absence. Unfortunately, Nefarian and Onyxia were killed by Horde and Alliance forces, respectively, leaving nobody behind to continue Deathwing's plans. Sinestra, on the other hand, wasn't beholden to Deathwing at all.
After the disappearance of Deathwing and the deaths of Nefarian and Onyxia, Sinestra reemerged hoping to continue her family's plan of creating a superior dragonflight to rule over Azeroth. So Sintharia traveled to Outland and made a deal with the orcs - trading the services of the black flight for netherwing eggs, and letting it slip that 'her master' could use them. Sintharia's visit to Outland can be seen in World of Warcraft: The Burning Crusade, in which Lady Sinestra appears as a level 73 NPC located at the Dragonmaw Base Camp in the contested territory of Shadowmoon Valley. She uses her blood elven guise for her meeting with Overlord Mor'ghor, presenting herself as an emissary of the black dragonflight.
Sinestra thought she was turning her back on her flight and creating a flight of her own; in reality, she was simply responding to the machinations and whispers of her former mate. Deathwing had his superior flight of dragons, for the caverns below Grim Batol were filled with eggs left over from Sinestra's experiments. He also had a method of creating more, something that is discovered in the Bastion of Twilight.
Despite her demise in Night of the Dragon, Sinestra has returned in World of Warcraft: Cataclysm. Now a ravaged husk of her former self, pieced together and reanimated by the powers of Deathwing's Old God master, Sinestra oversees the creation of new twilight clutches. She is the 'true' final boss encounter in the Bastion of Twilight in Grim Batol, accessible only after defeating Cho'gall on Heroic difficulty. It is revealed that she's giving birth to a clutch of black dragon eggs that are to be turned into twilight dragon eggs. She performs the duties once held by Alexstrasza in Grim Batol. Sinestra's fate, ultimately, is as an egg factory for Deathwing and the Twilight Cult, producing black dragon eggs to be turned into twilight eggs.
At the outset of the battle, Sinestra is weakened from past battles and from nurturing the Twilight brood. During the fight Calen also appears in his night elf guise. Sinestra siphons all the life energy from her eggs and shoots that energy at Calen. He dies and gives his power to the raid, giving them a buff that increases the party's haste by 100% which is enough strength to finally defeat Sinestra. She dies despite having 1 million health left, sinking into lava. Many fans believed she was still alive, until this was confirmed by both Blizzard and Deathwing himself to be false.