Hillary Clinton makes a speech on Cuban relations at Florida International University in Miami on Friday, calling for the lifting of the U.S. trade embargo with Cuba. (Joe Skipper/Reuters)

Calling the trade embargo against Cuba a relic of a failed Cold War policy, Democratic presidential front-runner Hillary Rodham Clinton on Friday challenged Republicans in Congress and in the 2016 race to finally do away with it.

“We have arrived at a decisive moment. The Cuban people have waited long enough for progress to come,” Clinton said. “Even many Republicans on Capitol Hill are starting to recognize the urgency of moving forward. It’s time for their leaders to either get on board or get out of the way.”

Clinton spoke in South Florida, for decades the heart of fierce and politically potent anti-Castro sentiment that has made the trade embargo untouchable, especially for Republicans. GOP candidates have it backwards on Cuba, Clinton said in remarks clearly aimed at former Florida governor Jeb Bush and Sen. Marco Rubio (R-Fla.), although she did not mention them by name. Both are among the most formidable Republicans also competing for the White House in 2016 and are staunch supporters of the five-decade-old embargo.

“We can’t wait any longer for a failed policy to bear fruit,” Clinton said to applause at Florida International University.

To a crowd in South Florida, Democratic presidential candidate Hillary Clinton outlined what she would do as president to change U.S. ties with Cuba. (Reuters)

Both Bush and Rubio have said the embargo gives the United States leverage against an abusive regime and have criticized efforts to remake the U.S.-Cuba relationship as naive.

Ahead of the speech, the Clinton campaign had blasted Bush and Rubio directly for clinging to what Clinton calls a failed policy of isolating communist Cuba.

“While a majority of Americans, including Republicans, understand that we must move forward, Jeb Bush and Marco Rubio refuse to learn from the lessons of the past that are in favor of failed isolationism,” campaign political director Amanda Renteria said. “This is why we must chart a different path forward in Cuba, betting on American influence to lift up the Cuban people.”

Bush responded in a Twitter message following the speech: “It’s insulting to many Miami residents for Hillary to come here to endorse a retreat in Cuba’s struggle for democracy.”

“Unilateral concessions to the Castros will only strengthen a brutal, anti-American regime 90 miles from our shore,” Rubio said in a statement ahead of the speech. “President Obama and Secretary Clinton must learn that appeasement only emboldens dictators and repressive governments and weakens America’s global standing in the 21st century.”

Two small groups of protesters stood across the road from the auditorium where Clinton spoke, shouting, “Human Rights for Cuba” and holding signs, including one that read, “No More Concessions to Castros.”

But the mood surrounding the speech, and Clinton’s own measured tone, suggested that the page is turning on ardent anti-Castro sentiment.

The trade embargo is part of a strict architecture of commercial and diplomatic separation imposed from the early 1960s in response to the communist revolution in Cuba, a short plane or boat trip from South Florida and a playground for American tourists for decades before the revolution.

With Obama’s second-term diplomatic opening to Cuba, the embargo is the last major pillar of that anti-Castro policy, installed by President John F. Kennedy and upheld by Democratic and Republican presidents ever since. President Bill Clinton strengthened the embargo following Cuba’s downing of private humanitarian planes from the Florida anti-Castro group Brothers to the Rescue.

But opposition to any engagement has been fiercest among Republicans and marked by years of political loyalties and political donations. The top donor to Bush’s super PAC is Cuban American Miami millionaire Mike Fernandez, who gave about $3 million to the group known as Right to Rise in the first half of 2015.

Clinton strongly supports Obama’s overture to Cuba, which has seen restored diplomatic ties and the easing of some travel restrictions. The embargo, however, would require congressional action to lift — something unlikely to happen at least until after the 2016 election.

Obama, and now Clinton, maintain that the embargo is a patent failure and gives the Castro regime an automatic excuse for the island country’s economic woes.

“The Cuba embargo needs to go, once and for all. We should replace it with a smarter approach,” Clinton said. She wants outreach to the Cuban private sector, among other things, because she believes that engagement and commerce will put pressure on the Castro regime.

“Today I am calling on Speaker Boehner and Senator McConnell to step up and answer the pleas of the Cuban people,” Clinton said. “By large majorities, they want a closer relationship with America. They want to buy our goods, read our books, surf our Web and learn from our people. They want to bring their country into the 21st century. That is the road toward democracy and dignity. We should walk it together.”

As a presidential candidate in 2008, Clinton had poo-pooed Democratic rival Obama’s proposal to reach out to Cuba as naive and premature. She would not commit to try to lift the embargo then. She announced a change of heart in her 2014 book “Hard Choices,” about her four years serving as Obama’s first-term secretary of state, and went further Friday.

The move reflects a decision that while there are areas of foreign and domestic policy where Clinton will seek to differentiate herself from Obama, this is one she will fully embrace. It is also a calculation that by casting Republicans as tied to a Cold War past that is foreign and mystifying to younger voters, Clinton can capitalize on a generational shift away from the Cuba hard line.

Public sentiment may be moving the same way, but that does not mean the embargo is likely to be lifted soon. A Pew Research poll from January found that 63 percent of Americans favored renewed diplomatic relations with Cuba and that about two-thirds want the embargo lifted.

A July Univision poll of Hispanic voters found that among Hispanics who say the issue of normalizing relations with Cuba would affect their vote, 2-to-1 said they would be more likely to support a candidate who favors normalization. The same poll surveyed Cuban-Americans nationwide and found that 40 percent said they were also more likely to support a candidate who favors normalization, with 26 percent saying the opposite.

Sentiment about the diplomatic opening and the embargo has been shifting steadily among Miami Cubans as younger generations born in the United States feel less of a connection to the powerful stories of persecution and desperation that marked their parents’ and grandparents’ views.

Clinton pledged Friday not to forget the tragic history of human rights abuses in Cuba, which Clinton and the State Department say continues today.

“Anyone who thinks we can trust the Cuban regime hasn’t learned the lessons of history,” Clinton said. She said she wants to maintain human rights sanctions on Cuba.

Clinton said that as secretary of state she came to believe that the embargo and diplomatic isolation strengthened the Castros’ grip on power and diluted American influence in the region.

Although most forms of U.S. trade are still banned under the 54-year-old embargo, a limited but growing number of American firms, such as food exporters and technology companies, are eligible to do business in Cuba. The online vacation rental site Airbnb has added more than 2,000 Cuban listings this year, and ferry companies and cruise ship operators are lining up to storm Cuba’s ports. A few consumers on the island are signing up for Netflix.

But many U.S. companies that would otherwise be eligible to do business there under Obama’s loosening restrictions still face daunting American regulatory obstacles — not to mention an opaque, state-run economy in Cuba that is no place for novices.

One of the most sensitive issues involves Washington’s support for opponents of the Castro government’s one-party system. Cuba vociferously objects to promotion of U.S. democracy, which it considers “subversion.”

Obama and Cuban President Raul Castro shook hands in April at a regional summit in Panama. It was the first meeting between a U.S. and Cuban heads of state since the two countries broke ties in 1961.

Secretary of State John F. Kerry will formally raise the U.S. flag at the reopened seafront U.S. Embassy in Havana on Aug. 14.