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The news of a No win in the Lisbon referendum has been greeted with disappointment but no real surprise by the Yes side.
Many politicians are already reflecting on the reasons behind a No victory with some pointing to an obvious 'disconnect' between the people and politicians.
It is a major blow to the Government and all the main political parties, except Sinn Féin.
The result also puts a question mark over how the EU moves forward, with most if not all of the other 26 countries likely to go ahead and ratify the treaty.
In general, working class and rural constituencies voted against the treaty, while middle class areas were in favour.
In a statement at Government Buildings, Taoiseach Brian Cowen said the Government accepted and respected the verdict of the Irish people.
Stressing that there will be no 'quick fix' Mr Cowen warned that there was no easy solution to the problem presented by the rejection of the treaty.
He said that as Taoiseach he took responsibility and said he would devote all his energies to resolving it.
Mr Cowen said rejection of the treaty means we are now in a position of considerable uncertainty.
Asked on RTÉ's Six One News if he was ruling out a rerun of the Lisbon Referendum, the Taoiseach said he wasn't ruling anything in or out.
He said he did not have an answer to what happens next, but would have to go to next week's European summit to see if there is a consensus on the way forward.
Ireland's decision to vote No has been accepted by European Commission President Jose Manuel Barroso.
He said 18 member states had already approved the treaty and the commission believed that the remaining ratifications should continue to take their normal course.
Mr Barroso said he had spoken to Taoiseach Brian Cowen, who told him the outcome should not be seen as a vote against the EU.
'The Lisbon Treaty is now dead' was the stark assessment by Labour leader Eamon Gilmore.
Mr Gilmore says his party will not support putting it to the people again.
The blame game is now under way among others in the Yes camp, with Fine Gael's Michael Noonan saying the No vote was a result of the Government campaign not starting on time.
He said it was a mistake to hold the referendum at this time just after a change of leader.
Minister for Foreign Affairs Michéal Martin said the Government would reflect on the result, but insisted all democrats in Europe would respect the decision of the people of Ireland.
Mr Martin admitted that people were in doubt 'and when in doubt…leave out.'
As the votes came in, Sinn Féin leader Gerry Adams stressed that the people had 'expressed concerns that needed to be dealt with - particularly that they want a social Europe.'
Declan Ganley of Libertas said there is now a clear mandate for Brian Cowen to go back to Europe with to look for a better deal for the Irish people.
Stressing that a No vote by the Irish people was not an anti-European vote, he said it will be the third time such a message will be sent to the elite in Brussels.
Munster MEP Kathy Sinnott also welcomed the No victory, saying the people of Europe will be delighted with the outcome as they were not given the chance to vote.
The 'disconnect' between the democratic voice of the people and their leaders was highlighted by Senator Shane Ross.
'We are now in an area the Government had not planned to be in' Sen Ross warned.
Earlier, Minister for Finance Brian Lenihan was heckled by No supporters as he tried to give interviews to the media at the RDS. He abandoned the interviews and was forced to leave the centre.
Former Taoiseach Garret FitzGerald spoke of 'a crisis for Ireland and for Europe'.
Mr Fitzgerald warned that Ireland has to face the fact that the other countries will want to go ahead with the ratification of the Lisbon Treaty and 'that is a real problem for us.'
Minister for Justice Dermot Ahern said 'this was Plan B' and said Ireland was now in uncharted territory. 'We will have to wait for reaction from the member states to this decision.'
Also calling for reflection was Fine Gael MEP Gay Mitchell, who said that all the issues involved in the campaign needed to be looked at.
He stressed that the argument put forward by others, that there was a lack of information about the treaty, did not stand up.
Irish Farmers Association President Padraig Walshe expressed his disappointment at the No vote but insisted that he did not think anyone voted against Europe or voted to damage the Irish economy.