England, the title holders, are 7-4 on favourites for a fourth championship crown in five years.
After lifting the Webb Ellis Trophy Down Under less than three months ago, head coach Sir Clive Woodward knows that huge expectancy now surrounds his World Cup heroes, even though the talismanic duo Martin Johnson and Jonny Wilkinson are both missing from the scene.
Legendary leader Johnson's retirement from Test rugby means that Lawrence Dallaglio is back at the helm for Sunday's opener against Italy.
Fly-half genius Wilkinson, meanwhile, will play no part in this season's championship after undergoing shoulder surgery.
But for Woodward, eager to draw a definitive line under the World Cup triumph, it is a case of onwards and upwards.
Sunday's sold-out Stadio Flaminio clash hands a golden opportunity to the likes of 32-year-old Northampton fly-half Paul Grayson, Bath captain Danny Grewcock, who replaces second-row giant Johnson, and Wasps flanker Joe Worsley, preferred instead of the axed Neil Back.
It is effectively the start of a new chapter in English rugby history, but RBS 6 Nations watchers should be braced for a familiar tale that points to red rose domination as their envious strength in depth is again showcased.
No-one illustrates the point better than 26-year-old Worsley.
First capped during World Cup 99, he has been in and out of the England team, finding it tough to break up an illustrious, record-breaking back-row unit of Back, Dallaglio and Richard Hill.
Back would find a way into most international teams, but just a slight dip in form has cost him his England place, such are Woodward's standards and expectations.
"I've started quite a few games in the past, but this is a huge opportunity for me. I am also very aware that there are guys chomping at the bit behind me," Worsley said.
"The pressure exerted by them on all of us to play well means that there is probably more pressure than being world champions or being England.
"The guys that have come into the team are so experienced, and have been in the England environment for so long, that we've got a fair idea of what is going to be required.
"The games you remember are not the 40-point victories, but games like against France in Paris two years ago when you are under pressure and up against it. That's when you learn what international rugby is about."