Paris - The Dutch rejection of a European pact with Ukraine is the latest popular vote to highlight anti-EU sentiment.
Britain is to hold a referendum in June on whether or not to remain in the European Union, a question with serious implications for the 28-member bloc.
National referendums have often determined the direction taken by the EU, whether by admitting new members, expanding its powers via treaty changes, or embarking on new projects.
While voters do not often say "no", leaders pay attention when they do. Here are examples: The European Economic Community's first expansion was in 1973.
Danish and Irish voters approved membership referendums, but Norwegians decided to stay out of the EEC.
In 1994 the Norwegians confirmed that decision in a second poll when Austria, Finland and Sweden joined what had since become the EU.
With a series of reforms and treaties, the EU has gradually expanded its powers and role, but some members must hold referendums on major changes.
On June 2, 1992, Danes shocked Europe when they turned down the Maastricht Treaty that established the EU and laid the groundwork for European monetary union.
They barely approved an amended version in May 1993 after Denmark was granted greater autonomy in defence, currency, citizenship matters and judicial cooperation.
The Treaty of Nice contained institutional reforms needed for the bloc's eastwards enlargement in 2004.
It faced a referendum in Ireland, where it was initially rejected in June 2001.
After obtaining guarantees regarding Ireland's cherished neutrality, a second referendum was approved in October 2002.
When asked to approve the European Constitution in May 2005, almost 55 percent of French voters said "non" and more than 61 percent of the Dutch rejected the draft three days later.
The Treaty of Lisbon replace the doomed constitution. Once again, Irish voters first said "no" in June 2008 before changing their minds in October 2009.
Two countries held referendums on joining the euro, which was created in 1999. In September 2000, just over 53 percent of Danes rejected the single currency, and in September 2003, neighbouring Sweden found that some 56 percent of voters wanted to keep their kronor.
Greek voters rejected in early July 2015 the terms of a third financial rescue plan proposed by the EU and the International Monetary Fund.
A week later, Greece and its creditors nonetheless agree to preliminary terms of a deal in return for reforms that exceeded those just rejected.
Non EU-member Switzerland voted in 1992 against joining the European Economic Area agreement linking the EU and other Western European countries and in 2001 voted against applying to join the EU.