Giffords could have stayed in office for another year even without seeking re-election, but her decision to resign scrambles the political landscape. Arizona must hold a special primary and general election to find someone to finish out her term, as well as hold the regular primary and general election later this year.
"I don't remember much from that horrible day, but I will never forget the trust you placed in me to be your voice," she said on a video announcing her decision.
Interspersed with photos, the video showed a close-up of Giffords gazing directly at the camera and speaking in a voice that is both firm and halting.
"I have more work to do on my recovery," the congresswoman said at the end of the two-minute-long "A Message from Gabby," appearing to strain with all of her will to communicate. "I have more work to do on my recovery. So to do what's best for Arizona, I will step down this week."
Giffords was shot in the head in January 2011 as she was meeting with constituents outside a supermarket in Tucson, Ariz. Six people died and Giffords and 12 others were injured. Her progress had seemed remarkable, to the point that she was able to walk into the House chamber last August to cast a vote.
The shooting prompted an agonizing national debate about super-charged rhetoric in political campaigns, although the suspect later turned out to be mentally ill.
With Giffords stepping down from her seat in southeast Arizona's 8th Congressional District, Gov. Jan Brewer will call a special primary election likely in April, followed by a general election in June. Before the cycle begins for the regular election, the district will be remapped and renumbered as the 2nd Congressional District.
The regular primary for the new district, which will cover most of the current district's territory, was scheduled for August.
The Republican governor acknowledged that the twin election cycles were going to create a mess, especially for potential candidates.
"I think that it's putting a lot of pressure on a lot of people awfully quick, given the fact that they're going to be filling that continuing seat that expires this year, and then we have elections coming (along) new congressional lines," Brewer said. "So there's going to be a lot of confusion in that congressional district."
Giffords would have been heavily favored to win re-election, since she gained immense public support as she recovered from the shooting. She was elected to her third term just two months before she was shot, winning by only about 1 percent over a tea party Republican.
A bevy of Republicans and Democrats have been mentioned as possible candidates for her seat, with several in the GOP already forming official exploratory committees. Republicans who have expressed interest include state Sen. Frank Antenori and sports broadcaster Dave Sitton, among others.
Democratic state lawmakers have been mentioned as possible candidates, as has the name of Giffords' husband, Mark Kelly, although he has publically quashed such speculation.