The two European giants will meet again in only their fourth competitive clash, and their second in this year's group stages, marking the first ever occasion Liverpool have faced Milan at San Siro.
But it won't be the first time the Italian club and stadium have had a profound effect on the city of Liverpool.
In April 1989, as a sign of respect shown to the 96 lives that were lost in the Hillsborough tragedy days earlier, a European Cup semi-final game between Milan and Real Madrid was paused.
The game is often recalled as a defining performance by one of the greatest club teams to bestride European football, as Milan took Madrid apart 5-0 to clinch their place in the final, 6-1 on aggregate.
But with exactly one minute of the game played, Belgian referee Alexis Ponnet blew his whistle to stop the match and prompt a pre-arranged minute's silence for the Hillsborough victims. It was a display of respect which may not be widely known these days, but was and still is remarkably moving to recall.
The silence among 73,000 supporters soon turned to applause from the San Siro crowd, before the supporters broke into a spontaneous rendition of the chorus of 'You'll Never Walk Alone' in recognition of those who lost their lives just a handful of days before.
Although 96 supporters lost their lives on the day, a coroner this year declared a 97th person had died following the passing of Andrew Devine who suffered brain damage on the day.
Football fans have long paid their respects to the fans who went to see their team play a match at Hillsborough on 15 April 1989, never to return home and this is one such act, which is often forgotten about.