Drusilla was sired by Angelus after he had met the human Drusilla in a confessional when she believed she was confessing her sins to a priest (who Angelus had just finished draining). The human Drusilla was suffering from visions that her mother had told her were sinful and from the devil.
Angelus became intrigued with Drusilla, and before turning her killed her entire family and made her insane. Drusilla as a vampire considered to have her visions, and she also played with her dolls (her favourite seemed to be Mrs. Edith.) She met the human William after he had been rejected by his friends, and the young woman that he thought he loved, for writing awful poetry, earning the nickname William the Bloody.
Drusilla turned William (who became known as Spike) stayed with Angelus and Darla until Angelus has his soul returned by gyspies. Once their vampire family was broken up, Drusilla and Spike roamed all over, causing mayhem, destruction and death becoming the Sid and Nancy of the vampire world. The relationship between the two vampires drastically changed after Spike allied himself with the Slayer in order to prevent Angelus from opening a portal to Hell, and ultimately so that Spike could steal Drusilla away from Angelus. Drusilla felt that Spike had become too soft and leaves him for a chaos demon. Spike returns to Sunnydale and Drusilla disappears for a while.
However, Drusilla does not stay missing for too long as she is brought to L.A. by Wolfram and Hart's lawyer, Linsdey McDonald, when the recently resurrected human Darla is dying of a STD and Angel refuses to turn her. Drusilla, however, has no qualms about turning her former grand-mother. Drusilla stays until L.A., until Angel burns both Darla and Drusilla. Drusilla briefly returns to Sunnydale again to tempt Spike to return to her again, but realizes that Spike is in love with the Slayer. She leaves Sunnydale and has not been heard from since.
Drusilla has only had three known relationships: the slightly disturbing relationship with Angelus who she calls Daddy, her relationship with Spike, and the chaos demon that she left Spike for. However, there are only two men for Drusilla, that would be Angelus and Spike, and she seems unaware or does not care about the jealousy that it causes between the two vampires.