European Union leaders will hold a videoconference on Thursday where they are set to discuss the vaccine roll-out and epidemiological situation, external relations and the bloc's digital strategy.
Transatlantic relations will also be high on the agenda, but this time with one difference: President Joe Biden will join the meeting via video link in what EU heads of state and government hope will be the moment to rebuild the alliance with the U.S. after four tumultuous years of Donald Trump.
Both sides have been trying hard to show their commitment towards renewing their partnership this week, with Secretary of State Anthony Blinken in Brussels to meet with NATO foreign ministers and top EU officials.
But with many other pressing issues on leaders' plates, here are four things to look out for as the summit gets underway.
The EU's vaccine rollout has come under sharp criticism for its considerably slow pace compared to other western countries, like the UK and US, so how this can be sped up will certainly be one of the main talking points, especially as some European countries are hit by a third wave of the virus.
Commission President Ursula von der Leyen is set to update leaders on the bloc's efforts to increase vaccine production and supply, but likely to dominate discussions is the newly-announced tightening of criteria to authorise the export of EU-made coronavirus vaccines.
The idea behind it is to secure supplies for citizens inside the bloc, which essentially means that countries like the UK - which the Commission says is not sending any jabs to Europe - could be blocked from receiving any inoculations if the EU decides to do so.
"We have to ensure timely and sufficient vaccine deliveries to EU citizens,” said von der Leyen. "The EU is proud to be the home of vaccine producers who not only deliver to EU citizens, but export across the globe."
She added: "But open roads should run in both directions."
German Chancellor Angela Merkel said Tuesday that the bloc must be "very careful" with any export ban, highlighting how difficult the discussion will be between the 27 member states that are divided on the issue.
Earlier this year, the EU imposed sanctions against Russian officials involved in the jailing of Kremlin critic Alexei Navalny, bringing relations between the two to a new low.
Leaders will discuss how to move forward on this, after also announcing new sanctions this week against China and other human rights offenders, leading Beijing to join forces with Moscow in a show of strength at a joint press conference Tuesday, where Chinese Foreign Minister Wang Yi and his Russian counterpart Sergey Lavrov condemned sanctions against them as "interference".
The situation in the Eastern Mediterranean involving Turkey will also be a key issue, but rather than discussing heightened tensions, like with Russia and the EU, leaders will talk about a recent thaw in relations, which has likely seen sanctions against Ankara avoided.
High Representative Josep Borrell and the Commission are expected to submit a report on EU-Turkey relations ahead of the meeting, which will propose a reset in relations with President Erdogan by offering a review of the migration deal that could include a fresh injection of European money.
However, the document will also present ways to keep Ankara from continuing with what the bloc describes as "provocative" actions.
The Commission laid out its digital strategy for the next decade earlier in March, which included proposals to ensure every citizen has access to high-speed internet at home or on-the-go by 2030, as well as training at least 80 per cent of adults in basic digital skills by the end of the decade.
Leaders will look at these plans, but will also review work on a digital tax, targetting companies like Apple and Google, which the EU would like to implement at an international level, including with its transatlantic partner the US.