The Kildare man's World Cup dreams were left in tatters at Murrayfield on September 6, 2003 when he broken his left leg after a heavy tackle from Scotland's Mike Blair.
Coach Eddie O'Sullivan called it "a dreadful injury at the worst time possible" as Ireland finalised their preparations for the 2003 tournament during which Murphy was set to be one of the team's star men.
Roll on four years and it has not been injury that has been keeping the 29-year-old out of the Irish team, it is loss of form. Murphy was badly caught out as he missed a tackle on Raphael Ibanez for a try in France's dramatic Six Nations win at Croke Park in February.
He failed to feature in the rest of the tournament and was not part of Ireland's matchday 22 for their Triple Crown-clinching success over the Scots at Murrayfield in March.
But towards the tail-end of the season, Murphy rediscovered some of his old form when helping English side Leicester Tigers to a domestic double and a Heineken Cup final appearance.
He saw game-time in both of Ireland's summer tour matches in Argentina and is itching to impress the Irish coaching staff this weekend in what the player himself views as "a final trial" for World Cup selection.
"When the team for this game was announced, I knew I was going to go back to Murrayfield. I thought a little bit about it (the leg injury from 2003). I'm a little bit nervous but I'm sure I'll get over that," Murphy admitted.
"But there's nothing really you can do about that. I think I probably will be nervous. It's a final trial before the World Cup squad is picked, and on top of that, I've the idea of breaking my leg four years ago in my head. I've just got to get on with it.
"It's a final trial game, there are places up for grabs and there are a lot of guys keen to put in good performances and hopefully get themselves into a World Cup squad. But I'm sure once the game starts it'll go straight out of my head."
Just as the Murrayfield leg break is vivid in his mind, so too is his error in letting Ibanez take him on the inside for an early try in that defeat to France.
"There's nothing really I can do about it (the Ibanez incident) now," said the Leicester star who was dropped for the next game against England.
"You have to move on. It was a big price to pay - that's the way it rolls for you sometimes. I made a mistake and I'll hold my hand up and that was it. I was in covering at the time. I wasn't supposed to play in that game and then someone got injured. I wasn't in the starting team from the start of the Six Nations.
"If you make a mistake when you're not solidly holding down a spot, you're in difficulty with your position."
During the Six Nations, Murphy did show sparks of how scintillating a player he can be - remember his spectacular kick and catch against Wales which led to a try for Brian O'Driscoll?
It is that player that Irish fans want to see boarding the plane to France, and Murphy's confidence is certainly back - helped in no uncertain terms by his return to form at club level.
"I probably did lose confidence (after the France game). I was very lucky when I went back to Leicester then to play games. Things were going well for the club and I was straight back as a starting squad player. The rugby was good and we played some exciting rugby and straight away I was back in and playing," he added. "Very quickly you get the confidence back when you're playing in big games."
Having had stints at full-back and out-half against Argentina recently, the versatile Murphy is keen to let his rugby do the talking on Saturday. He wants his 49th cap to be remembered for all the right reasons.
"I'm looking forward to Saturday. It'll be really nice to be back in the green. It should be a good game and I'm looking forward to getting it out of the way, and hopefully it goes well."