Not only was she the first woman to hold the position, but she was at the center of some of the biggest controversies of the Clinton administration. She also had weekly on-camera press conferences, raising her profile and creating an atmosphere of openness at DOJ, which has since become much more opaque, according to reporters who covered the department at the time.
As the daughter of a newspaper reporter, Reno had a respect for journalism and would often stop by the press room at DOJ, recalled ABC Senior Justice Correspondent Pierre Thomas, who covered the department during her tenure.
"A truly unique figure," said Thomas after her death Monday.
Myron Marlin, who was Reno’s chief spokesperson at DOJ, said that it was the day-to-day efforts at the department that stood out - emphasizing the importance of the law and what the law could do for everyday Americans.
“She was a remarkable woman who was fiercely independent, full of integrity, and tough as nails. And, she was absolutely committed to public service,” said Marlin, managing director with FTI Consulting.
Here is a look back at some of the major issues during her time as attorney general, the longest stint in the 20th century:
Branch Davidian Raid at Waco
While attempting to serve the warrants, law enforcement came under fire. Four agents and five Davidians died during the ensuing gun battle, beginning the start of a 51-day siege.
FBI immediately sent reinforcements, with more than 200 agents present nearly every day.
On April 19, just a month after she assumed office, Reno authorized the use of tear gas to force out the large number of people left in the compound. Fifty adults and 25 children were found dead in the ruins.
That same evening she went on "Nightline" to discuss the situation and her decision.
Whitewater Real Estate Controversy
Questions over whether Clinton, during his time as Arkansas governor, used his influence to keep a failing Savings and Loan business afloat owned by his business partner as well as whether he helped steer a questionable government loan to a business associate.
All the while, the White House was accused of stonewalling by refusing to release documents.
Republicans wanted the Clintons to be investigated, but feared that Reno and other DOJ officials were too close to the Clintons to be independent.
In 1994, Reno appointed a special counsel to investigate the Clintons' dealings.
During a press conference in 1994, she defended her decision saying, it was “clear that we must do everything we can to ensure public confidence in the investigation and to separate fact from speculation as rapidly as possible.”
Gonzalez's frightened face when agents entered his room was plastered across television and newspaper across the country.
He had been found floating off of Florida's coast in 1999, after the boat he was in with his mother capsized.
Gonzalez stayed with his uncle in Miami, but the 6-year-old boy soon found himself at the center of a tug of war between Cuba and the United States over whether he should remain in this country or be returned to his father in Cuba.
Reno made the decision to return Gonzalez to Cuba after federal authorities interviewed his father.
Her actions enraged the Cuban exile community in Reno’s home state of Florida, but said she must abide by the law. After months of legal battles with his family in the U.S., he was forcibly returned to his father in Cuba.
"It is not our place to punish a father for his political beliefs or where he wants to raise his child. Indeed, if we were to start judging parents on the basis of their political beliefs we would change the definition of family for the rest of time,” she said at a press conference in 2000.
On April 19, 1995,the two year anniversary of the Waco bombing, a massive truck bomb blew up the Alfred P. Murrah Federal Building in downtown Oklahoma City, Okla.
The blast killed 168 people, including 19 children, and injured hundreds more and caused hundreds of millions of dollars in damage to structures and vehicles in the downtown area.
At the time it was the largest terrorist attack on U.S. soil.
"This has been a tragic and heartbreaking day. I can tell you this: The FBI and the law enforcement community will pursue every lead possible and use every resource to bring the people responsible to justice," she said in a statement at the time.
Reno oversaw the charges that were brought against anti-government extremists Timothy James McVeigh, who was executed, and Terry Lynn Nichols is serving a life sentence.
"How could some people imply a moral equivalency between the government's efforts to save lives at Waco and the cruel and indifferent taking of lives in Oklahoma City? Such reckless comparisons are despicable and have no basis in the truth," she said at a law enforcement event a few months after the bombing.
-Jack Date and Serena Marshall contributed to this story.