Paris Saint-Germain, Real Madrid and Tottenham all have the odds stacked heavily in their favour heading into the second legs of their Champions League last-16 ties this week.
Thomas Tuchel's Ligue 1 heavyweights crafted a commanding 2-0 win over Manchester United at Old Trafford, with a red card for Paul Pogba compounding problems for caretaker manager Ole Gunnar Solskjaer, who must grapple with a hefty injury list in the French capital on Wednesday.
Borussia Dortmund are faltering at the top of the Bundesliga and they were overrun at Wembley last month, with Spurs establishing a 3-0 lead to take to Signal Iduna Park.
Ajax were unfortunate to end up beaten 2-1 by reigning champions Madrid in Amsterdam after a stirring performance, but two away goals mean Santiago Solari's men hold all the cards.
However, as the examples below demonstrate, things do not always pan out as you might expect in Europe's premier club competition.
Roma 3 Barcelona 0 (4-4 agg, Roma won on away goals), 2018
Eusebio Di Francesco's side are 2-1 up as they head to Porto in this week's other last-16 encounter, having reached the semi-finals last season.
They did so in incredible fashion, coming back from a 4-1 first-leg deficit to defeat Barcelona on away goals after a thrilling 3-0 win in front of their home fans.
Edin Dzeko, Daniele De Rossi and Kostas Manolas secured the 4-4 aggregate draw and sent the Stadio Olimpico into raptures, as Barca, who would go on to complete a LaLiga and Copa del Rey double under Ernesto Valverde, completely fell to pieces.
Barcelona 6-1 Paris Saint-Germain (6-5 agg), 2017
If United can score an early goal at Parc des Princes on Wednesday, the memories of this fixture will probably start to bring PSG fans out in cold sweats.
Barca were eviscerated during the first leg of this last-16 tie, going down to a 4-0 defeat in Paris that felt like a significant Champions League breakthrough for the Qatari-backed club.
At Camp Nou, Luis Suarez and Lionel Messi scored either side of a Layvin Kurzawa own goal, only for Edinson Cavani to grab what should have been a decisive away goal for PSG.
However, two quickfire Neymar goals – the second a highly controversial penalty after an apparent Suarez dive – levelled the tie at 5-5.
Then, in the fifth minute of stoppage time, Sergi Roberto struck to create a slice of Champions League history – no side had ever turned around a four-goal first-leg deficit before.
Deportivo La Coruna 4-0 AC Milan (5-4 agg), 2004
Deportivo were among Spain's major forces just after the turn of the century and one of their finest moments in Europe came in April 2004 when, despite being 4-1 down from the first leg of their quarter-final against AC Milan, they stunned the Italians at home.
Walter Pandiani, Juan Carlos Valeron and Albert Luque had Depor ahead on away goals before half-time, with Fran Gonzalez – the club's record appearance holder who played for them in the Segunda Division during the late 1980s – fittingly scoring the fourth to make sure of their passage.
Deportivo were eliminated by eventual winners Porto in the semi-finals, but this comeback stood as arguably the very best in Champions League history until Barca went one better.
Liverpool 3-3 AC Milan (AET, 3-2 on pens), 2005
That famous night in Istanbul. Liverpool found themselves on the end of a hiding at half-time in the 2005 Champions League final, as Paolo Maldini and a Hernan Crespo brace had the Serie A side 3-0 up.
But the second half proved to be one of the most iconic 45 minutes in Liverpool's history, with goals from Steven Gerrard, Vladimir Smicer and Xabi Alonso levelling the match up by the hour mark.
Milan then failed to hold their nerve in the penalty shoot-out, as Jerzy Dudek's wobbly legged antics in the Liverpool goal helped the Pole outsmart both Andrea Pirlo and Andriy Shevchenko after Serginho blazed the first kick over, resulting in the Premier League side lifting their fifth European title.
Manchester United 2-1 Bayern Munich, 1999
Solskjaer tried to evoke the spirit of 1999 at United this week and who could blame him? The Red Devils boss was the star turn in possibly the two most dramatic minutes in the history of European club football.
United were trailing 1-0 to Bayern in the 1999 final at Camp Nou, with Mario Basler's skidding free-kick into the bottom-right corner looking set to be enough for the Bavarian giants to end a 23-year wait for glory.
However, the United of Alex Ferguson's era could never be discounted until the final whistle and substitute Teddy Sheringham swept Ryan Giggs' shot into the bottom corner to bring the scores level in the 91st minute.
Solskjaer, playing his customary role of supersub, avoided the need for extra time, stabbing Sheringham's header from a David Beckham corner into the roof of the net as United completed an historic treble in astonishing fashion.
Monaco 3-1 Real Madrid (5-5 agg, Monaco won on away goals), 2004
Monaco were an unexpected member of the last eight in the 2003-04 Champions League and had seemingly been put in their place after losing 4-2 at Madrid in the first leg, even if Fernando Morientes – on loan from the Spanish giants – netted their second late on to give them a chance.
A Raul goal nine minutes before the break in the return leg in Monte Carlo made their task even tougher, but Monaco rallied admirably – Ludovic Giuly pulled one back on the stroke of half-time, with Morientes then adding a second just after the restart.
Giuly – whose performances with Monaco ultimately earned him a move to Madrid's bitter rivals Barcelona – grabbed the decisive goal midway through the second half to secure progression, with Didier Deschamps' side finally halted by Porto in the final.
Barcelona 5-1 Chelsea (AET, 6-4 agg), 2000
A 3-1 first-leg loss at Stamford Bridge – having trailed 3-0 – had Barca in danger of being on the wrong end of a major 1999-00 Champions League upset prior to the Roman Abramovich era, but in the return match the Catalans showed their true class.
Tore Andre Flo's 60th-minute goal was sending Chelsea through despite Rivaldo and Luis Figo scoring before the break, but Dani Garcia netted seven minutes from the end of regulation time to force the additional period.
Rivaldo then converted a penalty after Celestine Babayaro was sent off and Patrick Kluivert wrapped things up, crushing Chelsea's dreams.