At least 49 people were killed and 53 more wounded in what is now the deadliest mass shooting in American history. Democrats, led by President Obama, made a now-familiar call for tighter gun laws. Many Republicans simply expressed their condolences and condemned the attack while Donald Trump blasted Obama and Hillary Clinton for refusing to blame the violence on radical Islam.
Here's a look at how the political world responded to the attack.
Obama called the shooting an "act of terror" that served as a "sobering reminder that attacks on any American, regardless of race, ethnicity, religion or sexual orientation is an attack on all of us."
In remarks from the White House briefing room, Obama said, "No act of hate or terror will ever change who we are or the values that make us Americans."
He also waded into the gun control debate. The Orlando shooting rampage, he said, is a reminder of how easy it is for someone to get a hold of a weapon that could kill people in a "school, or a house of worship, or a movie theater, or in a nightclub."
"And we have to decide if that's the kind of country we want to be," Obama added. "And to actively do nothing is a decision as well."
The President was briefed Sunday morning by several officials, including FBI Director James Comey and Lisa Monaco, Obama's homeland security and counterterrorism adviser, according to the White House. He also ordered American flags to be lowered to half staff to honor the victims.
Vice President Joe Biden was also briefed on the shooting and canceled a planned trip to Miami, Florida, to attend a fundraiser for Democratic National Committee chairwoman, Rep. Debbie Wasserman Schultz
Biden "offered his prayers for all those killed and injured in the shooting and sends his condolences to all the families and loved ones of the victims," according to a statement from his spokesman.
Trump, the presumptive Republican nominee, said Obama was far too timid in his White House appearance. Trump called on Obama to step down from the presidency and challenged Clinton to ratchet up her language about terror threats.
"President Obama disgracefully refused to even say the words 'Radical Islam,'" Trump said in the statement. "For that reason alone, he should step down. If Hillary Clinton, after this attack, still cannot say the two words 'Radical Islam' she should get out of this race for the Presidency."
Trump's campaign canceled a planned rally Monday in Portsmouth, New Hampshire, "due to the horrific tragedy that has just taken place in Orlando, Florida," a campaign statement said. But the candidate will pivot the focus of a scheduled Granite State speech the same day. The speech will no longer focus on what Trump has called a litany of scandals involving Bill and Hillary Clinton. Now, according to a Trump campaign statement, it will "address this terrorist attack, immigration, and national security."
Trump initially responded to news of the shooting through a series of tweets, including one that noted his early condemnation of radical Islam.
"Appreciate the congrats for being right on radical Islamic terrorism, I don't want congrats, I want toughness & vigilance. We must be smart!"
Clinton's campaign issued a hard-hitting statement accusing Trump of politicizing the shootings.
"This act of terror is the largest mass shooting in American history and a tragedy that requires a serious response," said campaign spokeswoman Jennifer Palmieri. "Hillary Clinton has a comprehensive plan to combat ISIS at home and abroad and will be talking to the American people in the coming days about steps she would take to keep the country safe. In contrast, Donald Trump put out political attacks, weak platitudes and self-congratulations. Trump has offered no real plans to keep our nation safe and no outreach to the Americans targeted, just insults and attacks. In times of crisis more than ever, Americans are looking for leadership and deserve better."
Clinton and Obama postponed a rally scheduled for Wednesday in Green Bay, Wisconsin, which would have been their first joint appearance since she became the presumptive Democratic nominee last week.
Clinton echoed Obama's language in a separate statement Sunday, calling the shooting an "act of terror" and an "act of hate."
"For now, we can say for certain that we need to redouble our efforts to defend our country from threats at home and abroad," she said. "That means defeating international terror groups, working with allies and partners to go after them wherever they are, countering their attempts to recruit people here and everywhere, and hardening our defenses at home. It also means refusing to be intimidated and staying true to our values."
The LGBT congressional caucus issued a statement saying they were "horrified by the tragic shooting."
"Though details are still emerging, an attack during Pride Month against Pulse, an iconic gathering place for LGBT Floridians, has a particularly insidious impact on our entire community. Our thoughts and prayers are with everyone affected by this tragedy," said Roddy Flynn, executive director of the LGBT Equality Caucus.
Florida Sen. Marco Rubio said attackers like the shooter in the Orlando massacre are "the new face of the war on terror."
"They have said openly that they intend to target us here, and one of the hardest parts of this war is the individual who carries out an attack by themselves in a soft target like this, basically, in Orlando, Florida," Rubio said in a phone interview with CNN's Jake Tapper on Sunday.
A top Senate Democrat, Chuck Schumer of New York, wrote on Twitter: "Horrified and saddened by the appalling attack at Orlando LGBT nightclub. Praying for the victims and their families."
Sen. Elizabeth Warren, a leading Trump critic, tweeted a series of mostly positive messages. The Massachusetts Democrat didn't directly confront Trump, but criticized his message obliquely.
"That's the message of Pride. That's who we are. That's how we'll defeat hate, & how we protect America. #loveislove"
"America is strongest when we unite & celebrate our diversity. When we promote those values abroad & live them here at home. #loveislove"
The runner-up to Trump in the Republican primary field, Sen. Ted Cruz of Texas, issued a lengthy statement calling for all Americans to "unite in defeating radical Islamic terrorism."
"The next few days will be sadly predictable," Cruz said. "Democrats will try to use this attack to change the subject. As a matter of rigid ideology, far too many Democrats -- from Barack Obama to Hillary Clinton -- will refuse to utter the words 'radical Islamic terrorism.' They will claim this attack, like they claimed every previous attack, was isolated and had nothing to do with the vicious Islamist theology that is daily waging war on us across the globe."