Barcelona meet with Napoli in the Maradona derby, seventh heaven for Sevilla and a battle of the gods.
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Barcelona's meeting with Napoli in the Maradona derby is writ large, but there is plenty to get your teeth into besides.
Enterprise Rent-A-Car presents UEFA.com's guide to the stand-out stories.
Thursday 17 February
The second legs take place a week later, on 24 February.
Barcelona seeking a missing piece
Barcelona's presence has raised the profile of the UEFA Europa League knockout round play-offs considerably. Xavi Hernández's side are in unfamiliar circumstances as they take on Napoli and, as such, can make a little bit of history; the five-time European champions won the UEFA Cup Winners' Cup four times and the UEFA Super Cup three times, but the UEFA Cup/UEFA Europa League trophy has so far eluded them. They did, however, win its non-UEFA predecessor competition the Inter-Cities' Fairs Cup three times.
Xavi's charges side are not the only European royalty in this round. Of the 16 sides involved, only eight have not won a major continental club trophy: Atalanta, Braga, Dinamo Zagreb, Leipzig, Olympiacos, Real Betis, Real Sociedad and Sheriff. The other eight teams have eight European Cups, ten UEFA Cup/UEFA Europa Leagues, seven Cup Winners' Cups and nine UEFA Super Cups between them.
What are the knockout round play-offs?
The UEFA Europa League knockout round play-offs have been introduced for the first time this season. There are 16 teams involved: the eight runners-up from the UEFA Europa League group stage and the eight third-placed teams from the UEFA Champions League group stage.
Ties are played over two legs and will conclude on Thursday 24 February; the away goals rule has been abolished. The eight winners advance to the round of 16 draw on Friday 25 February (the eight group winners have already qualified for this); the eight play-off losers will no longer be involved in 2021/22 European competition.
Supporting cast need to step up for Dortmund
Dortmund will not have been thrilled at missing out on a place in the UEFA Champions League round of 16, and their hopes of making amends by scooping some silverware in this competition have suffered a blow with the news that talisman Erling Haaland is likely to miss their play-off first leg.
Rangers would surely have been aware that Haaland has already scored against Scottish opponents in this competition: twice in the course of a 3-0 aggregate win for Molde against Edinburgh side Hibernian in the third qualifying round in August 2018. The likes of Marco Reus and Julian Brandt have been regular scorers in the Bundesliga so will be expected to chip in while Donyell Malen has the chance to stake his claim in Haaland's absense.
Sheriff reaching for more stars
Moldovan title holders Sheriff have already left their mark on European football this season, kicking off their maiden UEFA Champions League campaign with a 2-0 win against Shakhtar Donetsk and an even more sensational 2-1 success at Real Madrid.
The Tiraspol side failed to make it to the next phase of that competition, but have had the huge consolation prize of making it to the spring phase of a European competiton for the first time, with 2010/11 runners-up Braga their guests. "There is a desire to move on," said Sheriff's Ukrainian coach Yuriy Vernydub. "We will prepare seriously and want to approach the matches in the best possible shape."
Who awaits in the last 16?
Crvena zvezda (SRB)
Eintracht Frankfurt (GER)
Spartak Moskva (RUS)
West Ham (ENG)
17 & 24 February: Knockout round play-offs
25 February: Round of 16 draw
10 & 17 March: Round of 16
18 March: Quarter-final & semi-final draws
7 & 14 April: Quarter-finals
28 April & 5 May: Semi-finals
18 May: Final (Estadio Ramón Sánchez-Pizjuán, Sevilla)