Lib Dem Sarah Olney has unseated former Conservative Zac Goldsmith in Richmond Park, with a spectacular by-election victory.
The Lib Dems say it is a victory for those seeking an alternative to "this Conservative Brexit government".
But what does it mean for Brexit, the parties and politics in general?
Here's what politicians and commentators are saying:
"This by-election that we have just had was not a political calculation, it was a promise that I made and it was a promise that I kept."
Lib Dem leader Tim Farron
"The message is clear: The Liberal Democrats are back and we are carrying the torch for all of those who want a real opposition to this Conservative Brexit government. This was a remarkable, come-from-nowhere upset that will terrify the Conservatives. A year and a half ago, their man won by nearly 40% and had a majority of more than 20,000. In one fell swoop we have wiped that out completely. If this was a general election, this swing would mean the Conservatives would lose dozens of seats to the Liberal Democrats - and their majority with it."
"This result doesn't change anything. The government remains committed to leaving the European Union and triggering Article 50 by the end of March next year. In addition, we will continue to take decisive action in the national interest to secure the UK's place in the world - supporting a third runway at Heathrow to secure jobs and business opportunities for the next decade and beyond. Commiserations to Zac Goldsmith on his defeat. We are sorry that he is no longer in the House of Commons."
Winning candidate Sarah Olney
"The people of Richmond Park and North Kingston have sent a shockwave through this Conservative Brexit government, and our message is clear: we do not want a hard Brexit. We do not want to be pulled out of the single market, and we will not let intolerance, division and fear win."
Downing Street spokesman
"There's been a by-election in Richmond, we've had the results. That is a matter for the constituents of Richmond. The British people sent a very clear message on 23 June for Britain to leave the EU. The government is now getting on with the job of delivering on those wishes and making a success of it."
Prof John Curtice, Strathclyde University
"This is certainly a by-election that was held in very propitious circumstances for the Liberal Democrats. It's not just a constituency where probably over 70% of people voted to remain [in the EU] in June but it's also a constituency that consistently from 1979... through to 2010 saw the Liberal Democrats get 40% or more of the vote. The truth is, if the Liberal Democrats could have chosen any constituency in the country in which to fight a by-election at the moment, Richmond would almost undoubtedly have been top of the list. That said however, the crucial thing about this result is since 2010 the Liberal Democrats have been unable to turn propitious circumstances like Richmond into by-election successes... What I think we see emerging out of this by-election... at least the Liberal Democrats are beginning to regain the mantle of the protest party of by-elections... [but] there's still a long way to go."
Dave Hill, The Guardian
"For Olney and her party, victory will feel like the next step on a national comeback trail in a region of the capital that used to be an orange stronghold. For London, it is a local reassertion of its people's disquiet over the turbulence triggered by the Brexit vote and the destructive mentalities it has unleashed. A freak of a by-election that risked being pointless has ended up as a restatement of some of the capital's most distinctive values. It won't be the last time the city makes its feelings known." Read more
Jacob Rees-Mogg, Conservative
"The Lib Dems are quite good at winning by-elections, but that doesn't lead to a fundamental change in the political firmament. It was 48 years between their victory at Orpington and them being part of a government. So these things work very, very slowly if they work at all. This was a vote on Brexit, it was a very strongly pro-Remain constituency. And there is understandably a disgruntlement amongst people who were very strongly pro-Remain that the majority of the country went against them."
John Rentoul, The Independent
"It was a big jolt on the road to Brexit, a sign that many of the 48% who voted Remain still want Theresa May to pause and turn back. The Liberal Democrat victory in Richmond Park is most unlikely to stop Britain leaving the European Union, but it makes the small chance of delay slightly larger." Read more
Conservative Foreign Secretary Boris Johnson
Mr Johnson, who also opposes the expansion of Heathrow Airport, declined to be drawn on what the Richmond Park by-election result means for Brexit, while giving a speech at Chatham House.
He said only that he was "sad" that his "great friend" lost: "[Zac Goldsmith] was heroic and principled in standing up for what he believed in on Heathrow expansion... He will be missed but he will certainly be back."
Christopher Hope, Daily Telegraph
"Zac Goldsmith was a victim of his own principles. He had made clear since becoming elected in May 2010 as Conservative MP for Richmond Park that he would quit over a third runway at Heathrow. When ever I saw him in Westminster I would often ask if he would stand by this pledge: he never wavered, insisting that he stood by his pledge. Mr Goldsmith viewed it in simple terms - he wanted to stand up for his constituents many of whom bitterly resent the noise of their planes flying every minute over their homes in south west London." Read more
Fraser Nelson, The Spectator
"Even I can't say I'm upset that Zac Goldsmith has lost his seat. For the last few days, now, my journey into work has been an assault course created by cheery Liberal Democrat activists campaigning in Richmond - they earned their victory. Not once did I see anyone campaigning for Zac Goldsmith. Not that I wanted to see any of them: this whole by-election was an elaborate hissy fit by Zac. Voters were being used as political props, to add extra theatricality to his flouncing out of the Tory Party. If he wanted to resign the whip to fight Heathrow, he should have done so. But to resign his seat and stand again put everyone to the trouble of having to vote again - it was an act of self-indulgence that was rightly punished by voters." Read more
Lord Ashdown, former Lib Dem leader
"I think it's a tremendous success for the Liberal Democrats, coming from the road crash of the last election, and for our leader as well. And I think it really does show the government [that] this headlong rush towards a hard Brexit, that will cost a huge amount of jobs, isn't the right way for the country to go."
Green Party co-leader Jonathan Bartley (whose party did not stand a candidate to boost the Lib Dems' chances)
"We needed to make a very clear statement against the regressive alliance of Conservatives and UKIP. And that's a win, against the regressive alliance. But it's also a win, I think, for a new politics of hope, a new way of doing politics. We've shown that parties can put aside their tribalism, and under our broken first-past-the-post system, where it ends up often... being the choice between two candidates, people want the opportunity to express how they feel and to channel their feelings at this time through a by-election."
Conservative MP and Leave campaigner Michael Gove
"I think one of the striking things about Richmond Park is that it is a part of the country that voted very heavily to remain during the referendum as the rest of the country voted to leave. So given that the Liberal Democrat candidate - and congratulations to her - secured less than half the vote in a 70% Remain constituency, I don't think we can interpret too much from this particular result about Brexit. This was a local by-election with specific factors. Congratulations to Sarah Olney, deep commiserations to Zac Goldsmith but it would be a profound mistake for anyone to over-interpret the result."