At the end of two hours, 40 minutes of outstanding tennis, ebbing and flowing throughout, Murray led 4-2 in the deciding set before finally wilting, succumbing 1-6, 6-3, 7-5 in an enthralling quarter-final. However, with first the French Open and then Wimbledon to come, Murray will still be encouraged that his game is approaching the level that he desires.
If it was not the kind of Nadal performance that will put fear into the rest of his rivals at this month's French Open, it was yet another example that getting the better of him on clay remains an altogether Herculean task.
During the first set and also for long periods of the third, Murray reminded everyone why there is no reason he should not be successful on clay. Ripping his backhand cross-court into Nadal's often vacated forehand wing reaped huge dividends and the Scot dominated the first set as the world No.1 dropped the ball too short too often.
It was only the second set Murray had won against Nadal on the red stuff but, for the third time this week, Nadal showed that if even if his game is not as imperious as it has been over the years, he will fight to the very last.
An early break in the second set settled the Spaniard's nerves but after levelling the match and then going up a break in the opening game of the third, he was reeling as Murray roared to a 4-2 lead.
The seventh game was crucial as Murray let Nadal back in and the relentless Spaniard was able to ride his momentum to level at 4-4.
When Murray saved three break points in the next game to move ahead again, it seemed that the Scot might just sneak a win of seismic proportions. However, as he has done so often in his career, Nadal held firm when it mattered and after an easy hold of his serve, he broke when Murray double-faulted and then served out with confidence to reach the last four. There the Spaniard will come up against Bulgaria's Grigor Dimitrov.
There have been questions asked of Novak Djokovic too, although any doubts that he is a live contender for the French Open this year were surely removed in Rome yesterday. The Serb, who missed last week's Madrid Masters with a wrist injury and whose state of mind had been in a cause for speculation before the start of the week, held off David Ferrer 7-5, 4-6, 6-3 to reach the semi-finals of the competition.
With Nadal showing signs he may be human after all on clay, Djokovic must have been ruing his luck when he suffered a wrist problem in Monte Carlo in April.
However, the Serb showed no signs of discomfort yesterday as he ousted the ultimate battler, Ferrer, and did so with some of the most gruelling, lung-busting tennis imaginable.
"It was the most physical match I had on clay this year," Djokovic said, which will have been no surprise to anyone who watched it. "I am really glad to overcome this challenge because David is a great competitor.
"I respect him a lot. We all know how good his record is on clay - the best after Nadal. Knowing that I am going to work for every single point of the match, coming out as a winner gives me a lot of satisfaction and confidence."
It took two hours, 32 minutes for Djokovic to break Ferrer's resistance, the penultimate point a 38-shot rally summing up the entire match and showing, yet again, how dogged and brilliant the Serb can be.
Having failed to serve out for the opening set, Djokovic broke Ferrer again to take the opening set but the Spaniard hit back to level, thanks to one break.
The third set was touch and go but it was Ferrer who buckled first as Djokovic broke for 5-3 and then just about held on for victory, despite suffering a double-fault on his first match point.
The world No.2 will now play Milos Raonic of Canada, who continued his surprising run of form in Rome with a 6-3, 5-7, 6-2 win over Frenchman Jeremy Chardy.
It was a little easier for Dimitrov to progress into his semi-final, with his progress towards the top 10 aided when German Tommy Haas retired after losing the first set. "I don't want to stop my progress here," added Dimitrov.