Warren Gatland's men will begin their campaign where last year's one finished in glorious style, at a packed out Millennium Stadium.
And with ten of the successful British & Irish Lions in their starting XV for the Championship curtain raiser, Italy certainly look to be up against it.
In their favour is the fact that Wales are traditionally slow starters in the tournament, their defeat at home to Ireland 12 months ago a case in point.
But Gatland, fresh from that historic Lions series win Down Under this summer, insists his side are going to hit the ground running this time around.
"I spoke to Rob (Howley) about last year, and he said what they struggled when they only had 19 players who could train," he said.
"This year we are in a pretty healthy state physically, ones who have got injuries are not too far away, so we hope that will have a positive impact on how we start.
"It's a tough tournament to win, it's a tournament of momentum and confidence and trying to get off to a good start.
"We are not afraid of physically taking on anyone, we back ourselves to stretch them and to play at the pace intensity we want to play at for the full 80 minutes."
Skipper Sam Warburton will be warming the bench on Saturday as he continues his return from a shoulder injury sustained in the autumn internationals.
That means Alun Wyn Jones will lead the troops out in Cardiff after his star turn as skipper in the third Lions test this summer.
His opposite man is Sergio Parisse, and as so often appears to be the case, the Italian talisman carries the weight of a nation on his burly shoulders.
But the Italian pack are not short of experience, Marco Bortolami in the second row will be joining Parisse and Martin Castrogiovanni in the centurion club this weekend while Mauro Bergamasco returns for the Azzurri to win his 96th cap.
Coupled with that experience however are some callow backs out wide, Angelo Esposito wins his first cap on the wing while Tommy Allan will start his first ever RBS 6 Nations game at No.10.
And after a superb 2013 campaign that saw Italy claim wins over both France and Ireland, head coach Jacques Brunel knows that they are up against it this time around.
"During the last RBS 6 Nations we had that balance between our creativity and our defence but then in the summer and autumn we lost our defence," he said.
"It will be very difficult to do better, not least because of the calendar, with trips to Cardiff and Paris to start with, and two out of five matches at home.
"We don't have any numerical aims, we've gone back to the content of matches, the goal is to rediscover satisfaction, improve our level of play, especially in defence."