Here, Press Association Sport takes a look at some of the main talking points surrounding this week's games.
Solskjaer's big test
When United were paired with PSG during the final days of Jose Mourinho's reign this tie was seen as nothing more than a formality for the French champions. How times have changed. United have since won 10 and drawn one of their 11 games under interim manager Ole Gunnar Solskjaer as a new mood of optimism has swept through Old Trafford. Solskjaer has made an impressive case for being given the job on a full-time basis in the summer. But his previous opponents in this competition, from his time at Molde, have been Ventspils of Latvia, Basel, Sligo and Legia Warsaw, and this two-legged tie presents a huge test of his tactical acumen. United are boosted by PSG being without the injured Neymar, while Edinson Cavani is also a fitness doubt. But can their defence stand up to France World Cup winner Kylian Mbappe?
Spurs stand-ins must step up
Tackling Borussia Dortmund was never going to be easy for Tottenham, even with Harry Kane and Dele Alli in their ranks. After all, Dortmund boasts the best defensive record in the Champions League this season, conceding just two goals and keeping five clean sheets from their six group games. But the loss of injured duo Kane and Alli has put the spotlight on the support acts as Spurs seek to make the Champions League quarter-finals for the first time since 2011. Fernando Llorente, Lucas Moura and Erik Lamela, if fit after missing the Premier League win against Leicester with a back spasm, all provide attacking options for boss Mauricio Pochettino. Much will depend on Christian Eriksen and Son Heung-min, who spent seven years in Germany with Hamburg and Bayer Leverkusen, and who scored five times in as many matches against Dortmund.
Much of Tottenham's pre-match analysis will have focused on the Dortmund threat who grew up close to home. Londoner Jadon Sancho began his career at Watford before moving on to Manchester City and then Dortmund in August 2017. The England winger has been a sensation since moving to Germany and is the youngest player to score in this season's Champions League at the age of 18 years and 213 days. Sancho is also in sparkling form after scoring one goal and setting up the other two in Dortmund's 3-3 Bundesliga draw against Hoffenheim on Saturday. Still six weeks short of his 19th birthday, Sancho is now the youngest player to score eight Bundesliga goals – and will be desperate to shine in his home city.
Four-time winner Gareth Bale returns to the Champions League fresh from reaching a personal landmark at Real Madrid. Bale's fitness is always a source of angst in the Spanish capital. But he continues to deliver on the pitch when available, and his goal in Real's 3-1 weekend derby win at Atletico was his 100th in the colours of Los Blancos. Real's hopes of defending a title they have won four times in the last five seasons were written off by many following the summer departure of Cristiano Ronaldo, indifferent early-season form and the October sacking of manager Julen Lopetegui. But Real head to Ajax on Wednesday after six wins and a draw in their last seven games, and knowing exactly what is needed to win this competition.
VAR to make debut
After being used at the 2018 World Cup and various league and cup competitions around Europe, Video Assistant Referees (VAR) will be introduced into the Champions League from this round of matches. VAR will be used in order to support the referee when making decisions concerning four match-changing situations – goals, incidents in the penalty area, red cards and mistaken identity. The VAR will inform the referee when there is evidence of a clear and obvious mistake in one of these situations. The referee will be able to use the review area next to the pitch to take a final decision. UEFA say the process will be communicated to the crowd using either stadium screens or the public announcement system. Cue plenty of fun.