With half the ties either level or close, the UEFA Europa League could be set for a first ever shoot-out, while holders Club Atlético de Madrid are among the teams in serious jeopardy.
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Club Atlético de Madrid, winners of two of the last three UEFA Europa League titles, are one of a number of high-profiles sides with work to do in order to avoid exiting the competition on Thursday.
Atlético fell to a 2-0 round of 32 first-leg home defeat by FC Rubin Kazan despite the Russian visitors being reduced to ten men before the break. It was the first time the team placed second in the Spanish Liga had lost at the Estadio Vicente Calderón this season, and they must now overcome the odds to keep their title defence alive.
Facing even more of an uphill struggle are SSC Napoli, who will need to become the first club in UEFA Europa League history to recover a three-goal first-leg deficit if they are to stop FC Viktoria Plzeň. The Partenopei are staring at elimination after succumbing 3-0 on home soil to the Czech hopefuls.
Olympiacos FC are in an identical position to Napoli following their 3-0 loss at Levante UD, who continue to impress on their tournament debut. The Greek contenders are one of just two sides fresh from the UEFA Champions League group stage who will begin the second leg in arrears. The others, CFR 1907 Cluj, trail FC Internazionale Milano 2-0.
Cluj's fellow Romanian outfit FC Steaua Bucureşti also have a job on their hands, being required to overturn a 2-0 deficit if they are to prevent AFC Ajax moving a step closer to the Amsterdam final in May. In contrast, Russian duo FC Zenit St Petersburg and FC Anji Makhachkala both enjoy two-goal advantages ahead of their respective trips to Liverpool FC and Hannover 96. Another Bundesliga club playing catch-up are Bayer 04 Leverkusen, who lost 1-0 at home to SL Benfica.
Meanwhile, the pick of the Valentine's Day opening instalments has its sequel in Rome, where S.S. Lazio will hold a slight edge over VfL Borussia Mönchengladbach after their added-time equaliser secured a 3-3 draw in Germany. As for Tottenham Hotspur FC, they travel to Olympique Lyonnais hoping for more magic from Gareth Bale, whose two free-kicks at White Hart Lane earned the north London outfit a 2-1 lead.
That meeting between Lyon and Spurs is one of eight ties to be either level or with the sides separated by a solitary goal at the halfway stage. Indeed, with the likes of FC Dynamo Kyiv and FC Girondins de Bordeaux due to resume at 1-1, and the tie goalless between FC Metalist Kharkiv and Newcastle United FC, a first ever UEFA Europa League penalty shoot-out could be imminent.