The Northern Hemisphere's showpiece international tournament returns tonight when the old enemy arrive at a red-hot Miillennium Stadium.
Recent history does not read well for the Red Rose nation, who have not won in Cardiff since 2003.
After a fortnight of talking, Wales and England face a game which could define their respective seasons.
In his two biggest selection calls, Warren Gatland has chosen Ospreys Paul James and Craig Mitchell as his props in place of injured first-choice pair Gethin Jenkins and Adam Jones.
And James Hook starts at full-back in place of the recently fit-again Lee Byrne.
Both coaches have downplayed the significance of the Lions props absence, with modern rugby seeing far fewer scrums than previously.
But Andrew Sheridan and Dan Cole will certainly be targetting their front row rivals.
The question of where to play Hook was the other dilemma Gatland faced.
And he has elected to play the mercurial back at 15.
The decision shows how desperate the Welsh coach is to have Hook on the field in any position, though it is questionable how much influence he can have compared to playing at 10 or 13.
Gatland has elected to maintain faith with Stephen Jones and Jonathan Davies in those pivotal positions.
The final blow to the Wales team was the injury piked up by Leigh Halfpenny on Monday.
Morgan Stoddart, so brilliant in attack, replaces the Cardiff Blues wing.
But England will certainly target his occasionally suspect defence.
And in a game which Welsh backs coach Rob Howley believes will be won by "inches, not yards", this could be vital.
While much of the talk in the media has been of the Welsh injury situation, there is a belief England's injuries affect their side more seriously.
The loss of Courtney Lawes and Tom Croft significantly reduces the strength of the English line-out, an area where Wales are strong.
The onus will thus be on Dylan Hartley to answer his critic Gatland with a mature performance at hooker, where his throwing has occasionally gone awry.
And the visitors are also without dynamic captain Lewis Moody, with experienced centre Mike Tindall leading the side.
While there is a chance the injuries to the Welsh props and English line-out specialists may have a bearing on the game, the battle at the breakdown remains the area where the game is most likely to be won and lost.
The Welsh back row appears more balanced than its English counterparts.
The speed of Dan Lydiate, power of Andy Powell and turnover ability of youngster Sam Warburton look a potent combination.
England seem somewhat one-dimensional in contrast, and much attention will fall on debutant Tom Wood.
He will hope for a happier experience than Matt Tait suffered on his debut back in 2005.
The clash between Lions scrum half Mike Phillips and the hugely talented Ben Youngs will also be intriguing.
Leicester Tiger Youngs has exploded onto both the club and international scene in the 18 months, and Phillips will need to return to the form he showed on the 2009 Lions tour.
Elsewhere in the back line, Toby Flood and Stephen Jones are both experienced campaigners, though Jonny Wilkinson lurks on the England bench having been in fine form for Toulon.
Gatland will hope his side may edge the battle in the centres, with Jamie Roberts certain to test rugby league convert Shontayne Hape.
The back three of both sides contains magic, and the battle between Wales record try-scorer Shane Williams and the up-and-coming Chris Ashton could be worth the entrance money alone for the sell-out 74,500 crowd.
With the sides evenly matched, the atmosphere rated by Martin Johnson as the most hostile in the Six Nations may have a bearing on the outcome.
This is a formative England side who will not have experienced what they will tonight.
And with Wales absolutely desperate for a win for the first time in eight games, they may get it.