Atlético Madrid became the latest side to thwart Arsenal's European ambitions, as goals from Antoine Griezmann and Diego Costa proved sufficient to give Diego Simeone's side a 2-1 aggregate win over the Gunners in the Europa League semi-final.
It means Arsène Wenger will finish his 22-year reign at Arsenal without a single European trophy to his name. This seems bizarre when we think of his sides' achievements in domestic football - including two Premier League and FA Cup doubles and an unbeaten Premier League season with the Gunners in 2003/04.
Yet Arsenal's latest disappointment will leave Gunners fans with an all-too-familiar feeling, as there is nothing new about their side coming close to triumph but ultimately falling short in Europe. They haven't won a European trophy since Alan Smith's volley gave them a shock 1-0 win over Serie A side Parma in the now defunct Cup Winners' Cup in 1994.
Here are six of Arsenal's most heartbreaking European defeats.
1. vs Galatasaray (UEFA Cup Final, 2000) - No Turkish Delight for the Gunners
Today's Arsenal fans could be forgiven for shedding tears of nostalgia when they think about the quality of the side which reached the UEFA Cup final in 2000.
With David Seaman (also known as 'Safe Hands') in goal, Tony Adams in central defence, Patrick Vieira in midfield and Thierry Henry and Dennis Bergkamp up front - not to mention the lightning pace of Marc Overmars on the wing - the Gunners had a combination of solidity and flair which the current Arsenal side can only dream of.
Yet even this formidable combination was thwarted by Galatasaray - particularly their Brazilian goalkeeper Claudio Taffarel, who made a succession of superb saves against Thierry Henry in extra time.
Then Croatia striker Davor Šuker and the normally unflappable Patrick Vieira both struck the woodwork in the penalty shootout, and Galatasaray became the first Turkish side ever to lift a European trophy.
2. vs Chelsea (UCL Quarter-Final, 2004) - Not Quite 'Invincible' in Europe
After Arsenal drew 1-1 at Stamford Bridge in the first leg of their UEFA Champions League quarter-final against Chelsea in 2004, few would have given the Blues much hope in the return leg at Highbury. After all, this was Arsenal's 'Invincibles' season, in which they cruised to the Premier League title without losing a game.
When José Antonio Reyes scored for Arsenal at the end of the first half of the second leg, the away side's task looked even more daunting.
Unfortunately for the Gunners, goalkeeper Jens Lehmann's hands proved to be rather less safe than Seaman's. The German failed to hold Claude Makelele's long range effort, thus gifting an equaliser to Frank Lampard.
Just as an entertaining and open encounter seemed to be heading to extra time, left back Wayne Bridge played an excellent one-two with Eidur Gudjohnsen and fired an unerring low shot past Lehmann, breaking the home fans' hearts.
3. vs Barcelona (UCL Final, 2006) - Henrik Larsson's Devastating Cameo Rescues Barca
Arsenal have never come closer to winning Europe's top prize than in 2006 - even though they played most of the match with ten men, after keeper Jens Lehmann was dismissed for a professional foul on striker Samuel Eto'o in the first half.
Against the run of play, the Gunners took the lead in the 37th minute, as defender Sol Campbell headed home emphatically from Thierry Henry's free kick.
Remarkable as it may seem after some of Arsenal's recent defensive displays, the class of 2006 defended their lead quite superbly against a magnificent Barcelona side. They even had opportunities to score a second, as Barça looked increasingly anxious.
Then veteran Sweden striker Henrik Larsson came on for La Blaugrana and turned the match on its head with two sumptuous assists in the space of four minutes. First he set up Eto'o with a delicate flick in the 76th minute; then he sent Juliano Belletti through on goal with a reverse pass in the 80th minute.
Belletti made no mistake, and Arsenal's dream was over for another year.
At least this time - unlike some others - Wenger's side could take pride in a truly valiant effort.
4. vs Liverpool (UCL Quarter-Final, 2008) - Walcott's Wizardry Is All in Vain
Theo Walcott is surely one of the most enigmatic and frustrating players in the recent history of English football. When you think about some of the extraordinary things he's done in his career - the hat trick against Croatia in 2008, or the match-winning performance against Sweden in 2012, for example - you can't help wondering why he hasn't done that sort of thing more often.
In the second leg of Arsenal's Champions League quarter-final against Liverpool in 2008, we were treated to another rare moment of Walcott magic.
When he came on as substitute at Anfield, his side were trailing 2-1 on the night and 3-2 on aggregate, and they had less than 20 minutes to avoid yet another European exit.
Cometh the hour, cometh the man. With little more than five minutes remaining, Walcott went on a barnstorming run from inside his own half, beating six Liverpool defenders and setting up Emmanuel Adebayor for a simple finish. It was a goal worthy of winning any match in any competition in the world.
Unfortunately for the Gunners, it didn't. Liverpool scored two late goals - including a debatable penalty - to leave Wenger's side frustrated once again.
5. vs Manchester United (UCL Semi-Final, 2009) - Gunners Outgunned by Ronaldo
After only losing 1-0 at Old Trafford in the first leg of the Champions League semi-final against Manchester United in 2009, Arsenal were optimistic that they could overturn the deficit at home.
That optimism went up in smoke pretty quickly at the Emirates. Unlike Chelsea in 2004 or Liverpool in 2008, the Red Devils snuffed out the Gunners' hopes in little more than ten minutes, as a simple finish by Ji-Sung Park and a stunning 40-yard free kick by Cristiano Ronaldo put United into a lead they would never relinquish.
Ronaldo's second goal - and United's third on the night - only emphasised the gulf in class which had formed between two sides who had once been closely matched. United broke at lightning speed after defending an Arsenal corner, and a fantastic move involving Park and Wayne Rooney was finished expertly by Cristiano Ronaldo, who gave Manuel Almunia no chance from close range.
Robin van Persie's late penalty for the home side was no more than an afterthought.
6. vs Bayern Munich (UCL Round of 16, 2013) - Brave Gunners Give Bayern the Fright of Their Lives
Arsenal must be sick of the sight of Bayern Munich. The Bundesliga giants have eliminated the Gunners from the Champions League at the first knockout stage on four separate occasions - including an eye-watering 10-2 aggregate thrashing in the 2016/17 season.
Yet it could all have been so different for Arsenal in 2013.
After suffering a disastrous 3-1 home defeat against Bayern, Wenger's side needed to pull off one of the biggest shocks in European football history to win by three clear goals - or to win by two and score four or more - at the Allianz Arena.
They couldn't have hoped for a better start. That man Theo Walcott was involved again, as his cross was converted from close range by Olivier Giroud in just the third minute of the match.
Bayern looked some way short of their best, but still forced some impressive saves from Lukasz Fabianski. As the home side increased the pressure in the second half, it began to look inevitable that they would equalise on the night, even though Arsenal were still creating presentable chances of their own.
Yet it was the Gunners who scored again, as Laurent Koscielny headed home from a Santi Cazorla corner with five minutes remaining.
A match which, on paper, ought to have been a formality for the Bavarians was in danger of turning into their worst nightmare. Buoyed by Koscielny's strike, Arsenal pressed for a third goal which would have seen them through to their first Champions League quarter-final for three years.
Unfortunately for Arsenal, it wasn't to be. Bayern went on to lift the Champions League trophy, and the Gunners were once again left wondering what might have been.
- 90Min