US Secretary of State Marco Rubio has spoken of a defining moment and a "new era" as he travels to Europe for a major speech to the Munich Security Conference.
Rubio will lead the US delegation at the first major global event since President Donald Trump threatened Danish sovereignty with a pledge to annex Greenland.
French President Emmanuel Macron has insisted Europe must prepare for independence from the US, while Nato Secretary General Mark Rutte has stressed that transatlantic bonds are as close and important as ever.
The war in Ukraine, tensions with China and a potential nuclear deal between Iran and the US are also on the agenda as the security conference gets underway.
Rubio is expected to avoid taking Vance's abrasive approach from last year but, when asked if he was planning to be more conciliatory, he told reporters that Europeans "want to know where we're going, where we'd like to go, where we'd like to go with them".
Hours before German Chancellor Friedrich Merz was due to open the Munich conference, Foreign Minister Johann Wadephul told German public TV that the aim was to define jointly what held Nato together and show the US that it needed Europe too.
President Macron will also address the conference on Friday, having told the World Economic Forum in Davos last month that now was "not a time for new imperialism or new colonialism".
After a week of turbulent domestic politics, Sir Keir Starmer will also travel to Munich, where he is expected to hold meetings with both Merz and Macron, before addressing the summit on Saturday morning.
Conference chairman Wolfgang Ischinger, in a report ahead of the event, said: "For generations, US allies were not just able to rely on American power but on a broadly shared understanding of the principles underpinning the international order.
"Today, this appears far less certain, raising difficult questions about the future shape of transatlantic and international co-operation."
The former German diplomat said the White House's foreign policy "is already changing the world, and it has triggered dynamics whose full consequences are only beginning to emerge".