Arsenal, Olympique Lyon and Villarreal try to venture into the unknown this week when the second legs of the Champions League quarter-finals take place.
To reach the last four of Europe's elite club competition for the first time, however, they will have to oust three Italian clubs dripping with European pedigree.
Arsenal are best placed, having earned a surprise 2-0 first-leg lead over Serie A leaders Juventus at Highbury last week.
Arsene Wenger's team have recovered their old verve in recent times, exemplified by their 5-0 thrashing of Aston Villa on Saturday.
"We don't concede, we score goals," under-stated the Frenchman. "The team is continuing to develop well."
In Turin on Wednesday he will look to striker Thierry Henry to hurt Juventus on the break. Arsenal will be anxious to discover if injuries to midfielder Cesc Fabregas and ebullient full back Emmanuel Eboue will prevent them playing.
Juventus need an early goal to unsettle Arsenal's relatively inexperienced team but will not be helped by the suspensions of Mauro Camoranesi and Jonathan Zebina, both sent off at Highbury, and ex-Arsenal captain Patrick Vieira.
Lyon failed to pierce the defence of six-times winners AC Milan in their goalless first leg in France but will have taken heart from the Italian side's embarrassing 1-0 defeat by Serie A strugglers Lecce on Saturday.
Tiago Mendes, scorer of the runaway French league leaders' winner against Troyes on Saturday, is suspended for Tuesday's match at the San Siro and they will look to returning midfielder Juninho and goalkeeper Gregory Coupet for inspiration.
Milan conceded their title bid was over after the Lecce loss but at least they were able to rest striker Andriy Shevchenko and Brazilian Kaka.
Villarreal must overturn a 2-1 deficit in Spain when Inter Milan visit for what is likely to be a cagey return leg on Tuesday if they are to clinch a tie against Arsenal or Juve in the last four.
FRUSTRATED BARCA
The Spanish side specialise in narrow victories and with an away goal in the bag 1-0 would be enough against Inter, who need to quell Villarreal's Argentine playmaker Juan Roman Riquelme and Uruguay striker Diego Forlan.
Inter have an injury doubt over Portuguese winger Luis Figo.
Last but not least, competition favourites Barcelona start at 0-0 in the Nou Camp on Wednesday against Portugal's Benfica.
Frank Rijkaard's gifted team were frustrated by a 10-man Real Madrid in a 1-1 draw at the Nou Camp on Saturday and a repeat of that result against Benfica would see Ronaldinho and company eliminated.
Barcelona midfielder Thiago Motta is a serious doubt with a groin injury.
The Portuguese won 2-0 at last season's winners Liverpool in the previous round and are promising a battle. "We'll have to be warriors," said French winger Laurent Robert.
The winners face AC Milan or Lyon.
