After Darth Sidious became aware of how powerful Count Dooku's apprentice Asajj Ventress had become, he ordered Dooku to have the aspiring Sith Lord killed. Asajj escaped however, and returned to her people. Mother Talzin welcomed Asajj back, and offered to assist her in getting revenge on Dooku. First Asajj and a pair of Nightsisters using a spell provided by Talzin to render them invisible attempted to assassinate Dooku, when that failed Talzin provided Asajj with an ally, the Zabrak Nightbrother Savage Opress, who Mother Talzin offered to Dooku as a new apprentice when in reality he was a sleeper agent for the Nightsisters.
Count Dooku became aware of Talzin's treachery and sent General Grievous to exterminate the Nightsisters. The General was successful in wiping out nearly the entire clan, with Talzin escaping into the spirit world mere seconds before Grievous could strike her down.
Upon Savage Opress's return to the now war-torn Dathomir with the mentally insane former Sith Lord, Darth Maul, Talzin greeted the two and brought them to her village where she used her magick to restore Maul's sanity and give him new prosthetic limbs, aiding him in his long quest for revenge.
It wouldn't be until much later when Talzin would finally attempt to fully return to the physical world, using a ritual which involved the sacrifice of Bardotta's Queen, Julia. The ritual was thwarted by both Representative Jar Jar Binks and Jedi Master Mace Windu, and Talzin was forced to return back to the spirit realm.
In her final attempt to return, Talzin projected to Maul, now the leader of the Mandalorian organization known as Death Watch. Together, the two orchestrated a plan to capture both Count Dooku and General Grievous, and once Dooku was brought to Dathomir, A force draining ritual was initiated, leading to a duel between Talzin and Darth Sidious, who had come to stop the Nightsister once and for all. Talzin was able to fully return to the physical world, but her rebirth was short-lived, as once Dooku joined the fight, Talzin got overwhelmed, and was struck down by General Grievous, ending her life for good.
It has also been revealed Talzin was the one who saved Darth Maul after his duel with Qui-Gon Jinn and Obi-Wan Kenobi on Naboo.