The result will set the tone for the rest of the tournament, and there will be a long, hard road ahead if the Welsh finish second best.
On the back of what happened during their final two games of the Rugby World Cup, it's even more important that Wales make the perfect start.
You can't harp on too much about those displays in Australia, especially since both matches ultimately ended in defeat, but Steve Hansen's players must carry that standard of rugby forward.
There is no doubt that both Wales and Scotland have brittle confidence, and there will be pressure on both sides. The clash at the Millennium Stadium is one which could go either way.
I am confident that the Welsh can win, but we could certainly have done without the injuries to Robin McBryde and Robert Sidoli.
McBryde was the most consistent performer at the World Cup, and Sidoli is by far our best line-out forward. That both will be absent is a massive blow, especially since Scotland's defensive line-out is so strong.
Wales' problems during the 2003 RBS 6 Nations were due in part to the fact that they were living off scraps of possession - we simply cannot afford to do that against the Scots.
The line-out could also be crucial with Chris Paterson lining up at number 10 for Scotland.
Paterson is a very talented footballer but he has the pressure of the captaincy on him, and if we can restrict his time and space off the line-outs then it will affect his ability to dictate play.
It is equally true to say that Scotland will fear the Welsh backs.
The Achilles heel of Matt Williams' squad is the lack of pace out wide and it is therefore imperative that Wales win the battle up front to secure plenty of ball.
That's where they have failed in the past, losing out in the physical battles among the forwards, and I'm sure it will be the crucial factor this time.
Meetings between Wales and Scotland tend to produce good rugby, and hopefully that will be true again.
But if the Welsh can produce the right result, they have another two home games to go, and their 2004 RBS 6 Nations could end up being a real success.