In 2000, incumbent State Representative Ken Pruitt successfully ran for a seat in the Florida Senate rather than seek re-election, which created an open seat in the 81st District, which included parts of Martin County and St. Lucie County.

Harrell ran to succeed Pruitt and defeated Genny Jackson in the Republican primary with 68% of the vote, advancing to the general election, where she faced Walter Sawyer, the Democratic nominee, whom she was able to defeat easily, winning 59% of the vote to his 41%.

In the general election, she won nearly 100% of the vote, only facing opposition from write-in candidate Robert Lilley.

She met a serious challenge to her re-election in 2006, when Bill Ramos, a mortgage broker, and the Democratic nominee, campaigned on "eliminating unfunded mandates from the state to the local level.

Unable to seek re-election in the legislature due to term limits, Harrell instead decided to run against Democratic United States Congressman Tim Mahoney in the 16th congressional district, running against Tom Rooney and Hal Valeche.

During the campaign, former 2008 Republican presidential candidate Mike Huckabee conducted an internet poll to determine whom his political action committee, Huck PAC, should support in the race.

"[5] The Palm Beach Post endorsed Fetterman over Harrell, praising the incumbent for closing a loophole that allowed sexual predators to avoid prosecution, and once again criticizing Harrell for her record in the legislature, where "she wasn't known for bucking the GOP leadership.