Two tournament favourites in Napoli and Tottenham face tricky second legs as they look to progress to the last 16 of the UEFA Europa League.
Rafael Benitez's side host Swansea at the Stadio San Paolo after a goalless draw in Wales, knowing a score draw would eliminate them on away goals, as well as a defeat.
Tottenham face arguably a greater task in overturning a 1-0 deficit against Dnipro of Ukraine when the two sides meet at White Hart Lane.
Yevhen Konoplyanka's late penalty earned the Ukrainian side a slender advantage in the first leg as the English side's 100 per cent record in the competition was snapped.
Should Tim Sherwood's side progress, they are likely to face last year's runners-up Benfica, who hold a 1-0 lead going into their home leg with PAOK.
Two sides expected to make it through are Juventus and Fiorentina, who both hold two-goal cushions over their opponents.
Juventus beat Trabzonspor 2-0 at home last week, while Fiorentina won 3-1 in Denmark against Esbjerg, and the Italian duo will face each other in the next round if they avoid a shock.
Lazio could not complete a trio of Italian winners however, as they went down to a 1-0 home reverse at the hands of Bulgarian outfit Ludogorets, leaving Edoardo Reja's men with it all to do in the return leg.
Valencia look set to progress, holding a 2-0 lead over Dynamo Kiev with the home leg to come, while AZ will also be confident after a 1-0 win in the Czech Republic against Slovan Liberec.
One team with a mountain to climb are Dutch giants Ajax, who have to somehow turn around a disastrous 3-0 defeat against Red Bull Salzburg in Amsterdam.
Local rivals domestically, Real Betis and Sevilla will look to boost the presence of La Liga teams in the last 16, with both earning score draws from away trips in the first leg.
Betis returned from Rubin Kazan with a 1-1 draw, while Sevilla's game at Maribor ended 2-2. If both sides progress, they would meet in a spicy last-16 tie.
Two sides knocked out of the UEFA Champions League, Shakhtar Donetsk and Viktoria Plzen, go head to head with the tie delicately poised following a 1-1 draw in the Czech Republic in the first leg.
Porto, winners of the tournament in 2011, let a two-goal lead slip at home to Eintracht Frankfurt last week to draw 2-2 and their misery was further compounded as an 81-game unbeaten run at the Estadio do Dragao was brought to an end by Estoril at the weekend.
Coach Paulo Fonseca has seen his future questioned in the aftermath of the defeat, and will be desperate for a win, though Frankfurt's two away goals will give them confidence.
Elsewhere the ties between Anzhi and Genk, Chornomorets and Lyon, and Maccabi Tel Aviv and Basel also remain finely balanced following goalless draws in the respective first legs.
|10||E. Adebayor||65' 69'|
|Coach: T. Sherwood|
for Sandro 76'
for A. Townsend 85'
for Soldado 88'
|Crouch happy to silence doubters|
|Blanc questions rivals´ mental strength as PSG gain ground|
|Kane: Fortune favoured Chelsea|
|Ancelotti defends Isco substitution|
|Rooney: Di Maria will come good|
|Stubborn Villarreal impress Real´s Pepe|
|PSG could not ´kill off´ Monaco - Van der Wiel|
|Serie A Review: Napoli suffer defeat at Torino, Lazio lurking|
|Ligue 1 Review: Title chasers´ slip-ups go unpunished|
|La Liga Review: Real and Atletico suffer frustrating draws|
|Primeira Liga Review: Porto´s Tello dents Sporting´s title hopes|
|Monaco 0 PSG 0: Champions miss chance to go top|
|Real Madrid 1 Villarreal 1: Moreno leveller ensures stalemate|
|Simeone satisfied with Sevilla point|
|Henry: Chelsea can win a trophy treble this season|
|Mancini frustrated by ´hesitant´ Inter|
|Sevilla 0 Atletico Madrid 0: Simeone´s men in fiery draw|
|Pochettino upbeat despite League Cup defeat|
|Inter 0 Fiorentina 1: Montella´s men end San Siro wait|
|Bundesliga Review: Wolfsburg edge eight-goal thriller, Monchengladbach win|
|Mourinho revels in ´beautiful´ League Cup success|
|Eredivisie Review: PSV lose home record as Ajax close the gap|
|Terry thrilled by ´massive´ League Cup final win|
|Chelsea 2 Tottenham 0: Mourinho´s men seal League Cup success|
|Coquelin sustains broken nose|
|Wenger hails Giroud character after Everton goal|
|Everton not getting what they deserve - Martinez|
|Coutinho is coming of age at Anfield - Rodgers|
|Football League Preview: Wolves in the hunt for back-to-back promotions|
|Norwich City 2 Ipswich Town 0: Neil´s men go third with derby triumph|
|Southampton v Crystal Palace: Fonte focusing on big picture|
|Arsenal 2 Everton 0: Giroud strikes to silence doubters|
|Dynamo Dresden v Borussia Dortmund: Hummels eager to build on derby win|
|Rodgers tips hat to relentless Liverpool|
|City facing uphill challenge to retain title - Pellegrini|
|Celtic 4 Aberdeen 0: Champions dominate top-of-the-table clash|
|Lallana hails ´massive´ win as Liverpool´s top-four charge continues|
|Hull City v Sunderland: Cattermole allowing no excuses against ´bogey team´|
|Liverpool 2 Manchester City 1: Coutinho dents City´s title hopes|
|Sunderland to appeal Brown red card|
|Aston Villa v West Brom: Sherwood looking for confidence boost|
|Allegri not taking risks on Vidal and Pogba|
|Pardew defends Jedinak over Sakho elbow|
|Heldt apologises after Schalke´s derby humbling|
|Milan must give that bit extra - Bocchetti|
|Rooney: Brown red must be rescinded|
|Monk hails Swansea´s versatility|
|Melbourne Victory 2 Wellington Phoenix 3: Hosts miss chance to go top|
|Rodgers: Top-four finish would be bigger than last season´s effort|
|Batman and Robin ´a bit of fun´ - Reus|
|Rakitic feeling better after ending goal drought|
|Copa Libertadores Preview: Well-rested Cruzeiro ready for Universitario|
|Fournier fuming after Lyon loss|
|DFB Pokal Preview: Gladbach visit rusty Offenbach|
|Mourinho: Tottenham approached me|
|Primeira Liga Review: Birthday boys Benfica hit Estoril for six|
|Inzaghi finds positives in lacklustre display|
|Eredivisie Review: AZ move third, Propper fires Vitesse to victory|
|Chievo 0 Milan 0: Pressure back on Inzaghi|
|Bundesliga Review: Derby win for Dortmund superheroes, Leverkusen go fourth|
|Ligue 1 Review: Lyon loss leaves door open for PSG|
|Bueno nets perfect hat-trick in four-goal spree for Rayo|
|Carver impressed with Newcastle´s fighting spirit|
|Van Gaal explains Di Maria decision|
|Luis Enrique angered by Granada pitch|
|Sherwood confident of Villa survival|
|Referee East says ´no mistaken identity´ as Poyet pledges to look again|
|League One Review: Robertson and Johnson off to winning starts, Bristol City go eight clear|
|Bruce angered by missed decision|
|Berahino can be ´top class´ - Pulis|
|Grateful Gutierrez thanks ´special´ fans|
|Monk targets Swansea points record|
|Klopp´s ´perfect´ afternoon|
|Victory soured by Ireland injury, says Hughes|
|Championship Review: Middlesbrough´s opportunity missed as Derby are defeated|
|Koeman: I am realistic on Champions League|
|League Two Review: Burton beaten again, Hartlepool gain welcome lift|
|´Triple punishment´ rule could be scrapped|
|Scottish Premiership Review: Inverness slip up as strugglers prosper|
|Mancini wary of Fiorentina quality|
|Hearts attack hits double figures in Scotland|
|West Brom 1 Southampton 0: Berahino wins it, then limps off|
|Manchester United 2 Sunderland 0: Rooney at the double amid red card controversy|
|Newcastle United 1 Aston Villa 0: Cisse strike downs visitors|
|Stoke City 1 Hull City 0: Super sub Crouch secures win|
|Granada 1 Barcelona 3: Suarez inspires routine win|
|Burnley 0 Swansea City 1: Trippier own goal proves decisive|
|Borussia Dortmund 3 Schalke 0: Late show seals dominant derby win|
|Referee Dowd fails to make it through West Brom, Saints clash|
|Allardyce ´shocked´ after home loss|
|Pardew lauds Murray after ´mixed afternoon´ for striker|
|West Ham 1 Crystal Palace 3: Pardew enjoys more away-day success|
|Blanc: PSG prepared for confident Monaco|
|Ancelotti: Isco place is non-negotiable|
|Pellegrini out to end dismal record at Anfield|
|Roma v Juventus: Matri eyes glory in title tussle|
|Martinez wary of wounded Arsenal|
|A-League Review: Spectacular Sydney derby the highlight|
|Perez to testify in corruption case|
|Bentaleb determined to avoid European hangover|
|Liverpool cannot dwell on Europa exit, says Rodgers|
|Marquinhos welcomes Manchester United interest|
|Tottenham must be ´nearly perfect´ to beat Chelsea - Pochettino|
|Bielsa: I take responsibility|
|League Cup final ´most important´ for Mourinho|
|Rodgers unsure if European exit will be a blessing|
|Vitoria Guimaraes 1 Maritimo 0: Hosts end winless run|