While encounters between the two club teams stretch back to 1891, in the regional era there has also been a rich history, most notably during the 2008-09 season.
That year Dai Young’s side played the Cherry and Whites three times and prevailed on every occasion – first at the Millennium Stadium, then with 14-men at Kingsholm and finally a 50-12 romp in the EDF Energy Cup final at Twickenham.
In European history Gloucester have the edge with three victories prior to that 2008-09 Heineken Cup double.
Fast forward eight years and the most recent chapter will be written at Kingsholm on Saturday night.
Danny Wilson’s men qualified for the knockout stages after winning five of their six games in Pool Four and go into the encounter with some confidence despite an agonising one-point defeat to Leinster last weekend.
Wilson has made four changes to that side with several big guns returning. Sam Warburton and Taufa’ao Filise both come back from international duty and injury respectively.
Gethin Jenkins steps up from the bench to reclaim the captaincy after coming through his comeback from injury unscathed while Lloyd Williams gets the nod ahead of namesake Tomos.
What they said:
Danny Wilson is pleased with the strength in depth the Blues currently have at their disposal and he is relishing the occasion.
“On the whole it’s a far healthier squad, and you saw that with the bench last weekend.
“We don’t have huge depth, but if we’ve got a healthy squad, as we’ve proven more than once this season, we can compete with anybody.
“The goal now for everyone concerned is a European trophy. If we were fortunate enough to get near that and challenge for it, it would be a great achievement for this group.
“We know there is no tougher game than going to a packed Kingsholm on a Saturday night to play a Gloucester side that are impressive, especially at home.
“These are the games you want to be in as a coach and a group of players and we've got that opportunity on Saturday night.
“Two sides from either side of the bridge makes for an exciting encounter. I hope we can show to our supporters how passionate we are for them to get an away win in a big European fixture.”
Sam Warburton makes his first appearance for the region since starring in the Six Nations and he is determined to clinch another piece of regional silverware.
"I love the fact that we have this European game now and something to play for at the end of the season. Top six was the target for us and that's looking difficult now but we have this to play for.
"I would love to get some more silverware at the Blues and this is a massive opportunity to do that. Whatever the competition, to have a quarter-final is fantastic.
"When we won this competition back in 2010 that was one of my top three, if not top club experiences. I have that medal in my little trophy cabinet and it's one I'm really proud of.
"It was an amazing day and experience for the club so if we can win this competition it would be massive and I would get a heck of a lot of satisfaction from that.
"People ask me about career targets and one of them is to win another trophy with the Blues. I have this season and have signed a contract extension so if I could win something at my home club that would be really rewarding.
"This is obviously a great chance to do that, all the hard work has gone in through the autumn and winter in to get us to the quarters and now is the chance you have to take."
Blaine Scully, who captained the Blues last week, has billed the game as the team’s “everything” and is looking forward to his latest encounter at Kingsholm.
"That is why you play, to have the opportunity to chase cups like this. This is now everything to us. It is where all our focus is.
"It will be pretty big, our biggest game of the year and a real raw opportunity for us to go out make a statement and put in a performance.
"Kingsholm is pretty unique and one of the great grounds. They obviously love everything about their rugby team, it's an energetic crowd and can be hostile but as a competitor that's a great place to go and compete.
"It's fun to be in that environment and feels like it's you against the world. You have to embrace that moment and enjoy it for what it - an amazing opportunity to play in a great ground, against a great opponent in a really meaningful game."
Nicky Robinson was of course involved in those three encounters with Gloucester in 2008-09 before joining the Cherry and Whites the next season.
You can read Robinson’s recollections in full here