Liverpool lost their first European penalty shoot-out as Dejan Lovren was the only man to miss from the spot against Besiktas in Istanbul.
There was no happy return to the Ataturk Stadium, where the Reds famously won the Champions League on penalties against AC Milan in 2005, as Brendan Rodgers' side exited the Europa League after a torturous affair.
On two of their three previous occasions Liverpool's success from the spot earned them a European Cup, on the other it was for a place in the final.
This occasion it was merely for a place in the last 16 of the Europa League but that should not have mattered.
But having conceded a 72nd-minute goal to substitute Tolgay Arslan to level the tie at 1-1 on aggregate Liverpool, shorn of eight senior players, had nothing left in the tank and looked dead on their feet after 120 minutes.
However, substitutes Rickie Lambert, Adam Lallana, Emre Can -- suffering from cramp -- and Joe Allen all converted their penalties but when Arslan scored Besiktas's fifth Lovren could not reply.
The 20 million-pound summer signing from Southampton has had a torrid start to life at Anfield, losing his first-team place after a couple of months, but it has now taken an even greater turn for the worse.
Extra time was the last thing Rodgers wanted as it meant his side landing back in the UK less than 55 hours before hosting Manchester City in the Premier League.
His players will take some lifting and some recovering after falling short in a competition they were one of the favourites for.
It also means their only route to regaining Champions League football is through a top-four finish in the Premier League, which makes the City game all the more important and the noon kick-off even more ridiculous from a scheduling point of view.
With that in mind Rodgers had left behind playmaker Philippe Coutinho so that meant Mario Balotelli, who scored the only goal at Anfield last week, was handed his first start since Nov. 8 and he immediately became the focus of attention.
His booking in the 11th minute was all his own making, chopping down Veli Kavlak as he tried to make amends for losing the ball in his own half.
But he took a fair share of the punishment Besiktas dished out to him, which appeared to be a cynical and not very subtle way of trying to get the temperamental Italy international sent off.
To his credit Balotelli kept his cool and kept plugging away, creating chances for Raheem Sterling and the best one of the first half for Daniel Sturridge, who having been guilty of overcomplicating twice already made it a hat-trick by opting not to shoot with his right foot with only goalkeeper Cenk Gonen to beat and eventually losing the opportunity.
Sadly they were about the only chances Liverpool created in 90 minutes as the burden of not conceding seemed to weigh heavier than scoring the important second goal in the tie.
But by half-time the deafening noise inside the Ataturk had been reduced to an acceptable level after a defensive performance much better than the one they had in the stadium almost 10 years ago -- although to be fair Besiktas are a pale imitation of AC Milan circa 2005.
Martin Skrtel, captain for the night in the absence of the injured Steven Gerrard and Jordan Henderson, led from the front and did well to clear Olcay Sahan's near-post cross with Demba Ba lurking behind him.
Lovren displayed equally good anticipation with a sliding interception to cut out a through-ball to the striker after Kolo Toure, in his first appearance since returning from the African Nations Cup, had lost possession with an aimless pass.
Goalkeeper Simon Mignolet comfortably dealt with shots from Sahan, Serdar Kurtulus and Jose Sosa either side of the interval as Besiktas began resorting to long-range efforts.
There were two more Skrtel blocks as Liverpool continued to smother the life out of the game, although Mignolet would probably have struggled had Arslan's drive from distance been inches the other side of his left-hand post.
He was helpless, however, to stop the next effort from Arslan -- who injected some much-needed energy -- after Ba's lay-off on the edge of the area in the 72nd minute.
Youngster Jordon Ibe made way for the more defensively-minded Javi Manquillo and Balotelli was replaced by the more possession-responsible Adam Lallana in the last 15 minutes, but had Ba's shot not cannoned back off the crossbar from a stoppage-time corner the Reds would not have reached the additional period.
Ba was denied by Mignolet in extra time and Besiktas looked most likely of the two to score but it came down to the lottery of penalties and fate dealt Lovren a nasty blow.