A year after her first appearance as a peacemaker in her husband's rivalry with Rey Mysterio, Vickie resurfaced in the summer of 2006 as a peacemaker in the feud between Mysterio and her nephew, Chavo Guerrero. After SummerSlam, Vickie turned heel and leveled Mysterio with a steel chair and allowed Chavo to attack him. At that point, Vickie became Chavo's business manager and the two of them tormented Mysterio as well as Chris Benoit.
Vickie's first heel role ended in 2007 when she became the Assistant General Manager of SmackDown, and later the permanent General Manager replacing Theodore Long. After that year's Survivor Series, Vickie became a villainess once again when it was revealed that she was in a romantic relationship with Edge, and she "punished" him for crashing the PPV's main event by making him the #1 Contender for the World Heavyweight Championship, which he would win at Armageddon. In her role as the heel General Manager of SmackDown, the evil Vickie made biased matches in Edge's favor and made life miserable for wrestlers such as Rey Mysterio, Batista, and even The Undertaker. After Taker won the World Title from Edge with the use of his Hell's Gate submission, Vickie banned the move, deeming it an "illegal chokehold," and stripped him of the title. She played a hand in ending Taker's career at One Night Stand, but after it was revealed that her now-husband Edge cheated on Vickie with their wedding planner, Alicia Fox, a vindictive Vickie reinstated Taker and put him in Hell In A Cell against Edge, all while displaying her now-trademark evil laugh
Vickie enlisted Big Show to take care of Taker in Edge's absence, but Edge would return in late 2008. In early 2009, it was revealed by John Cena that Vickie was in an adulterous relationship with Show. By that time, Vickie was not only running SmackDown, but Raw as well, but she quit due to the amount of embarrassment she suffered. At that point, Edge divorced her and humiliated her.
Vickie resurfaced as the Consultant to SmackDown GM Theodore Long in late 2009, and she wasted no time trying to overstep Long's authority. In her time as Consultant, Vickie hooked up with Eric Escobar and later Dolph Ziggler, while also aligning with LayCool (Layla and Michelle McCool) against Mickie James and Beth Phoenix. Vickie became interim GM when Long was attacked, and she made Dolph the top contender to the World Title, which was held by her ex-husband Edge. With revenge on her mind, Vickie banned Edge's spear from his arsenal, and tried to set him up as the one who attacked Long. It would turn out that Dolph was behind the attack and both he and Vickie would be fired by Long from SmackDown. Vickie later became the manager for Dolph and Jack Swagger, and has also returned to running SmackDown as well. She also feuded with AJ Lee during the latter half of 2012.
After Vickie put Roman Reigns in a battle royal for a spot in the WWE World Heavyweight Championship, she was on the receiving end of backlash from the evil Stephanie McMahon, who then challenged her to a match. Vickie accepted the challenge and made references to her late husband, Eddie Guerrero, which put an end to her lenghty run as a villainess. Vickie was defeated by Stephanie and later fired from WWE.
On July 4, 2016, Vickie returned to WWE for the first time in two years, doing so as a villainess and campaigning to become the new General Manager of SmackDown once the Brand Extension returns. During her promo, the evil Vickie bashed the other candidates and gave her evil laugh as she demanded that the fans help Vickie become the GM of SmackDown, before she was carried away by security. In yet another bit of humliation, Vickie encounted Dolph Ziggler for the first time in years, expecting him to save her; however, Dolph denied knowing her, and she was carried out by security.
- Vickie Guerrero is the mother of former WWE villainess Raquel Diaz.