Ronaldo and Messi are generally regarded as the two best players in the world, playing for arguably the planet's top two teams.
The two Spanish heavyweights have always had a healthy rivalry, but it is one that has become increasingly one-sided in the past few years.
Barcelona has been on a run of success that has seen the club win two Champions League titles in the past three years as well as three successive La Liga titles, while Real can lay claim to just the Copa del Rey crown won against the Catalan side last season.
But just as Barca has clearly become the superior to Real Madrid in recent years, the gap between Messi and Ronaldo has continued to grow as well.
However, Messi claimed the honor the next year when his Barcelona side beat Ronaldo's United in the Champions League final, with Messi netting the second goal in a 2-0 win.
And since that time, Messi has gotten the better of his Portuguese counterpart just about every time, with the latest example coming on Saturday in Barca's 3-1 win at Real Madrid.
Prior to Saturday's contest, the two teams had met seven times between league play, the Champions League and the Copa del Rey final.
Barcelona had won four of the seven games with two draws, while Messi had outscored Ronaldo 4-2 while assisting on two more goals.
But Saturday offered Real and Ronaldo a chance to turn around momentum in the rivalry as the hosts entered the match with a three-point lead and a game in hand on Pep Guardiola's side in the La Liga table.
And things couldn't have started better for Real as Barca goalkeeper Victor Valdes made a terrible pass from his own penalty area that handed Karim Benzema a goal after 22 seconds.
Ronaldo had a great chance to double the lead just before the half-hour mark but badly scuffed a shot from inside the penalty area, only to watch Messi turn around and set up the equalizer one minute later.
Messi had a relatively quiet match by his standards, but another glaring miss from Ronaldo in the second half with his team trailing by a goal looms large.
Xabi Alonso delivered a perfect cross to Ronaldo for a free header from six yards, but he nodded the ball wide and once again saw his miss punished immediately, killing off the game.
The result moves Barca level on 37 points with Real and gives you the feeling that this season will be no different from the past two, with Ronaldo and his team piling up plenty of goals but ultimately coming up short against Messi and his mates.
Ronaldo has been accused of being selfish on the field in an effort to regain his status at the best player in the world. But maybe the most effective way for him to regain that label would be to help Real Madrid beat Barcelona.
Not only did he miss two glaring chances, but his free kicks were subpar and he was the recipient of whistles from the home supporters, who no doubt have grown tired of being second best in Spain.
Ronaldo has presumably also grown sick of Messi's trophy haul, but he will in all likelihood have to watch the diminutive winger accept yet another award on January 9 as the FIFA Ballon d'Or honor will be handed out.
After all of the votes for the award are tallied Ronaldo will probably find himself in second place, a spot he is becoming used to.