At the 2004 U.S. Olympic Trials, Hoelzer qualified to swim the 200-meter backstroke by placing first, with a time of 2:11.88. She also swam in the 100-meter backstroke, but did not qualify to swim that event at the Olympics.
In the 2004 Summer Olympics in Athens, Greece, she placed 5th in the 200-meter backstroke, with a time of 2:10.70.
At the U.S. Trials on July 1, 2008, Hoelzer qualified to swim in the 100-meter backstroke at the 2008 Olympics. On July 5, 2008, Hoelzer broke her former Auburn University roommate Kirsty Coventry's world record of 2:06.39 in the 200-meter backstroke with a time of 2:06.09, ultimately qualifying for her second event in the 2008 Olympics. This record was broken in Beijing by Coventry. She also qualified for the women's 4x100-meter medley relay.
Hoelzer won a bronze medal in the 100-meter backstroke on August 12 in Beijing. She also won the silver medal in the 200-meter backstroke on August 16, and the silver medal in the 4x100-meter medley relay on August 17 after swimming in the qualifying heats for that event.
Hoelzer has revealed that she was sexually abused as a child. She said she shared her story to prevent future incidents of sexual abuse. Hoelzer is the national spokesperson for the National Children's Advocacy Center, and has received the "Voice of Courage" award from the Darkness to Light organization.