AC Milan and Barcelona, having cantered untroubled through the group stage, finally face testing opposition this week as the Champions League resumes following a two-month winter break.
Titleholders Barcelona, who averaged four goals per away game in the group stage, should find the going a lot tougher when they visit Bayer Leverkusen on Tuesday, the scene of their last defeat in Germany.
Milan host Arsenal on Wednesday and will be painfully aware that their last three participations in the tournament have ended in the last 16 at the hands of English Premier League opposition.
APOEL Nicosia, who visit Olympique Lyon on Tuesday, and Zenit St Petersburg, who host twice former winners Benfica in the freezing Russian winter on Wednesday, are the only newcomers to this stage of the tournament.
The remaining four ties will be played on February 21-22.
The line-up for the round of 16 has a familiar look with eight of the teams having reached the same stage last year.
France, Spain, England, Italy and Germany are represented as usual, joined by clubs from Russia, Cyprus and Portugal, instead of Ukraine and Denmark last time around.
Manchester United were the only one of the favourites who failed to make it past a group stage which has generally become a formality for the top sides with frequent one-sided contests.
AC Milan and Barcelona faced each other in the group stage but were untroubled by Viktoria Plzen and BATE Borisov as they both qualified with two matches to spare.
Barcelona are unbeaten on their last seven visits to Germany, their last defeat coming against the same opponents in the 2000-01 season.
Leverkusen, although unimpressive in the Bundesliga, won all their home games in Group E as they qualified at the expense of Valencia.
Serie A leaders Milan lost 3-2 at home to Barcelona in the group stage, with both teams having already qualified, and Arsenal coach Arsene Wenger has promised to follow Barca's example by attacking at the San Siro.
"You always have to push for a goal when you play away in the first leg because it gives you a cushion for the second leg," said the Frenchman whose side eliminated Milan at the same stage three years ago and are in the last 16 for the 12th season in a row.
"We will try to score, of course - we always do. The system rewards the audacious away from home."
Seven-times champions Milan subsequently lost to Manchester United in 2010 and Tottenham Hotspur last year.
Benfica, with a largely South American team, are likely to face temperatures well below freezing when they visit Zenit St Petersburg.
The Russians may be rusty, however, as it will be their first competitive match since the winter break.
In the other tie, there is a vast gulf in experience between Olympique Lyon, who are in the last 16 for the ninth time in a row, against APOEL, the first team from Cyprus to reach this stage.