Now, it's former Secretary of State Hillary Clinton and Vermont Sen. Bernie Sanders alone in the party's top tier of 2016 candidates.
There's no doubt Biden's decision will help Clinton's poll numbers more than Sanders' in the short term.
Polls have consistently shown Biden siphoned most of his support from Clinton. A CNN/ORC poll last week showed that Clinton held a 16 percentage point lead -- 45% to Sanders' 29% -- with Biden in the race and drawing 18% support. But with Biden removed from the list of candidates, Clinton's lead widened to 23 percentage points, at 56% to Sanders' 33%.
Sanders has sought to run to Clinton's left. Biden, meanwhile, would have staked a claim on the legacy of President Barack Obama -- attempting to inherit much of the coalition that had swept him into office twice while also appealing to older blue-collar voters.
Unless someone like Maryland Gov. Martin O'Malley shocks the political world by climbing out of the low single digits in the polls, Clinton now has a one-on-one race for the Democratic nomination.
Still, longer-term, Biden's exit could help Sanders: He's now the only high-polling Democratic alternative to Clinton, which means if she stumbles or voters sour on her campaign, he stands to be the sole beneficiary.
Expect a more tightly managed race
A Biden candidacy might have transformed the Democratic primary into a more free-wheeling campaign.
Biden himself has admitted he's known for saying what he means -- which isn't exactly the reputation of Clinton, who's seen as stage-managed to a fault.
Neither perception is entirely true: Biden, after all, is still a politician and subject to focus-group tested remarks. Clinton, meanwhile, has sought to bring a looser style to the trail, delivering a comfortable and confident performance in the first Democratic debate and poking fun at herself by appearing on NBC's "Saturday Night Live."
But without Biden in the race, there's less potential for off-script moments.
Clinton's dance with the White House gets less awkward
Though Clinton had publicly said she was giving Biden all the room he needed to decide, there were signs her campaign was preparing to run against the vice president.
She had staked out several policy positions that are at odds with the White House in recent weeks -- particularly on the Trans-Pacific Partnership.
Clinton opposed the massive Pacific Rim trade deal, siding with labor unions that have fought to block its implementation. Her position put her on the same side as Sanders, and would have forced Biden into an uncomfortable spot: He could support the Obama administration or side with his allies in labor unions, whose support he'd badly need in the 2016 race -- but not both.
Splitting with the White House is tough enough for a former secretary of state. It would have been much more difficult for a sitting vice president.
It's OK now for Democratic candidates to bash Republicans
When Democrats met for their first debate last week in Las Vegas, Clinton drew laughs when -- after being asked about the enemies she was proudest of making -- she mentioned Republicans.
It played well with liberals who are frustrated that Congress has attempted to block the Obama administration at every turn.
But Biden saw it as evidence of a poisoned political atmosphere, and criticized Clinton's tone.
"The other team is not the enemy," he said Tuesday night during dinner remarks at the Four Seasons hotel in Washington. "If you treat it as the enemy, there is no way we can ever solve the problems we have to."
When Clinton, Sanders and others lay into Republicans at upcoming presidential debates, Biden -- with his experience cutting deals with the GOP in recent years -- could have held them back. Now, the leash is off.
Even so, Sanders responded to Biden's point, on Wednesday, saying, "I would not use the word 'enemies' to describe fellow Americans," he said.
Things got a whole lot easier for President Obama
The prospect of a Biden-Clinton match-up was already causing heartburn at the White House, where loyalties run deep to both Democrats. Most of Obama's aides saw Clinton as the best positioned to carry on Obama's legacy, given her longstanding status as the party's presumed candidate.
Biden is a popular figure among administration officials, considered deeply loyal to the boss and admired for his perseverance in times of deep personal grief. But instead of inspiring hope that he would made a bid for the nomination, his public deliberations prompted worry he could damage his own standing as an elder statesman.
Obama said publicly many times he would give Biden room to make the decision himself, and lauded his No. 2 as the "finest vice president in history."
But without Biden in the race, it is clear Clinton becomes the candidate most likely to carry on Obama's legacy -- leaving the White House's loyalties no longer in limbo.