The Queen will shake hands with Sinn Fein's Martin McGuinness in a gesture that will herald a major milestone in Anglo-Irish relations.
Stormont's Deputy First Minister - a former IRA commander - and the Queen will join for a historic meeting in Belfast before making the symbolic greeting. The handshake has been hailed as hugely significant by peace campaigners, while republican Mr McGuinness said it would reach out to hundreds of thousands of unionists.
Peter Sheridan, chief executive of Co-operation Ireland, a charity which promotes peace in Northern Ireland and the Republic, said the gesture would alter things irrevocably.
"From my perspective it's a huge act of reconciliation, you cannot underestimate how important this is," he added. "Whoever would have thought we would ever be in this situation - I think it says a lot about healing, human dignity and treating each other with respect.
"I think after today all of us will say things have changed - for me that's the significance of it."
The Queen last year broke down barriers on both sides of the Irish border through her conciliatory words and gestures during her visit to the Republic.
Wednesday's meeting with Mr McGuinness - the first-ever between the monarch and Sinn Fein - will take place at a Co-operation Ireland event at the city's Lyric Theatre with the handshake being made in private alongside a handful of VIPs.
First Minister Peter Robinson welcomed the meeting, but acknowledged it would be difficult for the Queen, given that her own family was hurt by republican violence when the IRA killed Lord Mountbatten in a 1979 bombing in Co Sligo. The Democratic Unionist leader added that republicans should pay due respect to the monarch as a recognition of her importance to many in Northern Ireland.
The Queen, who will be joined by the Duke of Edinburgh, is joint patron of Co-operation Ireland along with the President of Ireland, Michael D Higgins. The President will be present at the event along with Mr Robinson. Leading figures from the arts have also been invited including Northern Ireland actor Adrian Dunbar who has appeared in notable films like My Left Foot, The Crying Game, and The General.
The meeting with Mr McGuinness is separate to the Queen's two-day Diamond Jubilee visit to Northern Ireland, which on Tuesday saw her and Philip tour Enniskillen. On Wednesday the royal couple will travel to Stormont in Belfast for a garden party attended by 22,000 guests in the grounds of the famous building.