Kenny Dalglish will manage Liverpool in Europe for the first time at Sparta Prague on Thursday in the Europa League.
The 59-year-old Scot's first six-year reign in charge of the Merseysiders started after the 1985 European Cup final, when a deadly riot led to them being banned from continental competitions for six years.
Dalglish returned to the club a month ago and the Europa League is his team's last realistic chance of winning of a trophy this season.
"It's his first game in Europe as manager of Liverpool and he's certainly had to wait a long time for it," said Ian Rush, a former teammate of Dalglish. "As a player he achieved so much in Europe. To win the European Cup three times is a remarkable achievement and he was a key part of Liverpool's domination.
"He was just very unlucky that when he was manager the first time around we were banned from Europe."
Dalglish will have to get used to Europe's second-tier knockout competition, with Liverpool unlikely to return to the Champions League next season.
Liverpool travelled to the Czech Republic for the last-32 first-leg match without captain Steven Gerrard and defender Daniel Agger, who have groin injuries. Midfielder Christian Poulsen will also be missing after his wife went into labour, but Joe Cole returns after overcoming a knee problem.
"There's no point being irresponsible with any of the players at this moment," Dalglish said. "If it causes them a bit of a problem we are as well nursing them through."
A 1-1 draw at Wigan at the weekend halted Liverpool's run of four straight Premier League wins, but the Reds revival under Dalglish has lifted the team to sixth in the standings away from the relegation zone.
"Kenny believes in the players, he believes we've got a good team and a good squad," defender Glen Johnson said. "He just wants you to go out and express yourself within the boundaries he sets. He almost says, 'Once you've crossed that white line it's up to you.'"
While forward Luis Suarez is ineligible after playing for Ajax in the Champions League group phase, Raheem Sterling could become Liverpool's youngest player if the striker, who scored five on Monday in Liverpool's 9-0 rout of Southend in the FA Youth Cup, plays at 16 years and 71 days.
Liverpool's match in Prague is one of 15 Europa League matches on Thursday since Manchester City played on Tuesday, drawing 0-0 at Aris.
Villarreal, who are fourth in the Spanish league, travel to Napoli looking for their first win in Italy.
Walter Mazzarri's side are second in Serie A, just three points behind leaders AC Milan thanks largely to Uruguay striker Edinson Cavani's 20 goals.
He has also scored five in the Europa League - a haul matched by Villarreal forward Giuseppe Rossi.
But they were both surpassed by Radamel Falcao's seven goals for FC Porto in the group stage. The Colombia striker has been out with a left-knee injury since January 16 but is set to return on Thursday at Sevilla.
While Sevilla are eighth in La Liga, Porto are performing strongly in Portugal, enjoying an 11-point lead while still unbeaten.
Three of Porto's rivals are also in action, with Benfica hosting German side Stuttgart, Braga at Lech Poznan in Poland and Sporting Lisbon in Glasgow at Rangers.
Ajax, who dropped out of the Champions League like Rangers, makes the short trip to Belgium to face Anderlecht, whose biggest threat comes from forward Romelu Lukaku.
"I will have to play smart not physically against him because he's very strong," Ajax defender Toby Alderweireld said. "We know he's strong and quick when he plays deep so we will have to hold him up."
Lille, who top the French standings, host PSV Eindhoven, while second-placed Paris St-Germain go to Belarus to face BATE Borisov.
Bayer Leverkusen will leave their German title ambitions to one side – they are second in the Bundesliga behind Borussia Dortmund – when they face to Metalist Kharkiv, whose Ukrainian rivals Dynamo Kiev are at Besiktas of Turkey.
Russia has four teams remaining in the competition, with two travelling to Switzerland: Spartak Moscow play Basle and Zenit St Petersburg, who are the only team to win all six group stage matches, face Young Boys.
CSKA Moscow are at PAOK Thessaloniki and Rubin Kazan host Dutch champion FC Twente.