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.
What to look out for?
Barcelona have amassed so much silverware over their 122 years that their trophy cabinet long ago made way for an entire room. But the distinctive UEFA Cup/Europa League prize is not among the hoard. They are four-time losing semi-finalists, but even the last four feels a long way off after being drawn with Serie A high flyers Napoli, pitting together the top-ranked teams in each seeding pot.
Barcelona are still adjusting to life without Lionel Messi but this tie brings to mind another mercurial Argentinian: Diego Armando Maradona. He played for Barça between 1982 and 1984 before leaving for Napoli and achieving immortality by winning the UEFA Cup, among other things. The second leg will take place at a stadium that now bears his name.
Sérgio Conceição's Lazio connection
Sérgio Conceição is also held in great affection at Lazio, where as a crowd-pleasing winger he lifted the UEFA Cup Winners' Cup and won the double in a two-season spell around the turn of the century. "It's going to be an emotional tie for [him]," says former Porto goalkeeper Vítor Baía. "He's part of the history of that great club."
Vítor Baía also has fond memories of the Biancocelesti: he was in the Porto side that beat them in the semi-finals en route to winning the 2003 UEFA Cup.
Seventh heaven for Sevilla
Sevilla's love affair with the UEFA Europa League would surely be dismissed by any self-respecting Hollywood producer as being too fanciful. A side with a solitary Liga title to their name have reached six finals in 16 seasons, winning them all: twice as many as any other side has managed!
Their single-minded determination is summed up by sporting director Monchi: "When we were eliminated [from the Champions League], our thoughts turned to the Europa League while still in the changing room." Dinamo Zagreb will not make it easy, though, and Sevilla have identified Mislav Oršić as the dangerman.
• Rangers take on a Dortmund side including Giovanni Reyna, whose father Claudio played for the Scottish club between 1999 and 2001.
• On-loan Real Sociedad forward Alexander Sørloth will be in familiar surroundings as he returns to Leipzig to face his parent club.
• It is a season of firsts for Sheriff. They were Moldova's maiden Champions League group stage representatives and now break new ground for the country by extending their European campaign into the new year.
• An Atalanta side named in honour of a courageous huntress from Greek mythology take on Olympiacos, named after the home of the Greek gods. Strap yourself in for some puns and clunky references, every journalist's Achilles' heel.
• Spanish sides have dominated this competition over the past two decades, winning 11 times. Sevilla and Barcelona will garner a lot of attention but, as their early-season form proved, Betis should not be discounted.
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)