Liverpool will fancy their chances, Spurs will try & dent Man City's quad quest and Man Utd will try and stop Barcelona, while Juve sweat on the fitness of Cristiano Ronaldo.
It's a huge week of European football as the first legs of the Champions League quarter-finals take place and there are plenty of talking points to chew over for these big games.
Here's the big issues surrounding the first legs this week.
United's Barca challenge
Ole Gunnar Solskjaer's Manchester United pulled off a shock to beat Paris St Germain in the last round and it was probably that result that clinched the manager's job full time for the Norwegian. Performances since have tailed off slightly and the challenge ahead of them as they face Barcelona and, of course, Lionel Messi, is huge. Barca are closing in on an eighth LaLiga title in 11 years and will be keen to make the most of Real Madrid's elimination from the Champions League.
City's quadruple push
Manchester City are the favourites for the Champions League and with good reason given their sustained excellence in four competitions this season. Manager Pep Guardiola described the quadruple as "almost impossible" at the weekend but it is actually far from inconceivable. The Champions League has been the one hurdle they have consistently failed to clear, however. Guardiola has often referred to a lack of experience on the European stage for that, although that may not be relevant in this round as they face a Premier League rival in Tottenham.
All-English clash
City's tie with Spurs is an enticing one, starting with the first leg at the London club's new stadium on Tuesday. City's superiority is evident in the 16-point gap between the two sides - from second to third - in the Premier League but a big domestic advantage counted for nothing when they faced Liverpool at the same stage last year. Then City lost 3-0 in the first leg at a fevered Anfield. Spurs will hope the atmosphere at their new stadium will work in their favour, although Kevin De Bruyne has dismissed it. "I don't care about the stadium," he said.
Liverpool eyeing last four again
Last year's beaten finalists Liverpool may fancy their chances of reaching the last four again after being drawn against Porto, a side they beat 5-0 in the first leg of their last-16 tie last season. The Reds' priority may be the Premier League but defeat here would represent a big missed opportunity. Porto are also without veteran defender Pepe for Tuesday's first leg at Anfield through suspension.
Ronaldo fitness
Five-time world player of the year Cristiano Ronaldo has been out for the past two weeks with a thigh injury but is expected to return for Juventus' clash with Ajax. Manager Massimiliano Allegri took no risks against AC Milan at the weekend, holding the Portuguese back in a bid to ensure his fitness for Wednesday in Amsterdam. Ronaldo, who has won this competition five times, relishes such occasions.