Clinton ran in the 2008 president election, ultimately narrowly losing the Democratic Party's nomination to Barack Obama despite beginning the primary season as the front-runner.
Her announcement comes at an auspicious juncture for her presidential aspirations. Although she departed Foggy Bottom with high approval ratings, renewed questions about her character and trustworthiness have surfaced amid a scandal involving the use of a private email server to conduct government business.
The scandal has taken a toll on her poll numbers: recent surveys show Clinton is the prohibitive favorite to win her party's nomination. However, she is now running neck and neck with virtually every major Republican challenger in key "swing" states—vote-rich places that often switch between support for Democratic and GOP candidates and are considered critical to winning the White House.
In anticipation of her announcement, potential Republican opponents have sharpened their attacks on Clinton's record and perceived trustworthiness. Kentucky Senator and GOP presidential hopeful Rand Paul said on Sunday that the former top U.S. diplomat's role in the death of four Americans in Benghazi, Libya during her tenure cast doubt on her ability to serve as commander in chief.
At a speech before the National Rifle Association just days ago, Texas Republican Senator Ted Cruz, the first officially declared candidate of the 2016 election cycle, excoriated both President Barack Obama and Hillary Clinton on the issues of foreign policy and gun rights.
Separately, former Florida governor Jeb Bush—who has yet to declare his own widely expected bid—released a video through his political action committee that said the country "must do better than the Obama-Clinton foreign policy that has damaged relationships with our allies and emboldened our enemies.''
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As Secretary of State, Clinton won plaudits for her focus on empowering women worldwide and promoting commercial ties as a form of American soft power. She has drawn criticism, however, for a lack of any signature agreements or breakthroughs during her tenure.
Others have criticized Clinton's handling of the 2012 attack on a consulate in Benghazi, which saw the death of a U.S. ambassador and three other Americans. Some lawmakers accused the State Department of severe security failings and claimed Clinton participated in a subsequent cover-up.
Meanwhile, questions have swirled around the finances of the Clinton Foundation, the massive philanthropy run by the former president, the Secretary of State and their daughter Chelsea. The organization's acceptance of foreign contributions, some during Clinton's tenure as Secretary of State, has ignited widespread concerns about conflicts of interest.
Despite the looming controversies, a 2016 Clinton presidential run has seemed inevitable to many in the Democratic party. Most national polls cite her as an easy favorite for the Democratic nomination—even after a recent furor over her use of a private email server while at Foggy Bottom.
--Reuters contributed to this report.