History does not favour Manchester United. On the two occasions they have attempted a comeback after a European first-leg defeat at Old Trafford - against Bayern Munich in 2001 and AC Milan four years later - they have lost the away leg as well.
Add to that another depressing statistic that shows the Red Devils have won only two of their last 19 games in Spain, and the challenge that awaits last season's Champions League finalists is clear for all to see.
Sir Alex Ferguson was full of praise for Athletic Bilbao after their shock 3-2 victory at the Theatre of Dreams last week, and as his players prepare to enter the San Mames stadium ahead of tonight's Europa League last-16 second leg encounter, the United boss is under no illusions about the difficulty of the task that lies ahead.
"It's going to be difficult for us," admitted Ferguson in his pre-match press conference. "Bilbao have a tremendous advantage winning at Old Trafford, but it's a challenge that is not beyond us.
"Our record away from home in Europe helps us, we've done very well in the last few years, but we're going to need a very good performance."
Five years ago, Manchester United did overturn a first-leg deficit, beating Roma 7-1, but that came on home soil and their task is not made any easier by the fact that Bilbao are unbeaten in 12 games at "the Cathedral".
Renowned for its policy of fielding only Basque players, or players groomed through its youth system, the club embodies a city which prides itself on its working-class values and distinctiveness from the rest of Spain.
Managed by veteran Argentine coach Marcelo Bielsa, and powered by a golden crop of youngsters, Athletic currently lie fifth in La Liga - one point behind the Champions League places - and have a Copa Del Rey final showdown with Barcelona to look forward to.
Confidence is understandably high, and there is a growing sense of optimism that the club's trophy drought, which stretches back to 1984, may be about to end. United's mission will not be made any easier by the fact they will have to contend with Bilbao's 12th man - the home supporters provide a hostile atmosphere in a bubbling cauldron where the stands virtually spill onto the pitch.
In anticipation of tonight's highly charged tie, GMF considers five of the other most venomous European stages...
5. Red Star Stadium, Belgrade
Home to Red Star Belgrade and more commonly known as the 'Marakana', this 55,000-seater stadium has been one of the most hostile environments to play football for nearly 50 years.
This Serbian fortress has witnessed 19 league championships and 18 national cups, but will soon close its doors as a New Red Star Stadium is currently under construction, and will hold an additional 15,000 raucous Red Star Ultras.
4. Signal Iduna Park (Westfalenstadion), Dortmund
The Temple of the Yellow Wall is one of the great sights in European football. The South grandstand, or 'die Sudtribune' holds over 25,000 of the total 80,000 capacity.
It's this enormous, steep-banked stand that generates most of the stadium's legendary atmosphere making it one of the most intimidating away grounds to visit.
3. Stadio San Paolo, Naples
Like all Italian football fans, the Neapolitans are passionate people, which makes for a raucous and equally intimidating atmosphere in the country's third largest stadium with a capacity of over 78,000.
Blue flares, banners, and fans draping over the enormous upper tier curves. helps to create a wall of noise and a real theatre of adrenaline.
With an exciting brand of attacking football currently on display in southern Italy, future success will mean that like the nearby Mount Vesuvius, Napoli's stadium is a Volcano waiting to erupt.
2. Stadion Miejski, Krakow
The home of Wisla Krakow has a reputation as being one of the deadliest venues in world football, thanks in no small part to the White Star's intense rivalry with inner city rivals Cracovia.
The area in Poland has seen one of the highest totals of football-related deaths in recent history - a reputation earning the nickname the "City of Knives".
1. Ali Sami Yen Stadium, Istanbul
It may have held little more than 25,000 fans, but Galatasaray's Turkish cauldron was widely regarded as one of the most poisonous venues in all of Europe.
Its location in Istanbul's roughest and toughest urban area, known as the Mecidiyekov, gave the club and its ground the complete and total intimidation package.
But, as the need for more revenue increased, the stadium closed in 2011 and Galatasaray fans are busy building the same famous atmosphere at their new home, the 50,000 capacity Turk Telekom Arena.