Just a few short weeks after Jerzy Dudek helped the Reds to their 2005 UEFA Champions League success with a penalty save from Andriy Shevchenko, the Pole was replaced by a then-22-year-old Spaniard from Villarreal.
Rafael Benitez, Liverpool's manager, labelled Reina as the best goalkeeper in Spain and immediately installed him as the first-team stopper.
There were ups and downs during Reina's first year at Anfield; as he adjusted to life in the Premier League he was encouraged to punch crosses clear rather than catch them. While this made for spectacular viewing at times, there also led to the odd clanger.
Reina more than proved his worth though and was a big factor in the Reds proving themselves one of the best teams in Europe for a spell thereafter as he won the FA Cup in his first season, reached the Champions League final in his second and won three successive Golden Gloves awards.
Imperious in dominating his penalty area, a great organiser of his defence and reliable in his handling, Reina was a foundation for the team to build from and was so consistent with his fitness that he played every single league game for four consecutive seasons from 2007-08 to 2010-11.
Since that final season of the run, however, Reina's form has been in something of a steady decline.
During the 2009-10 campaign when Liverpool dropped out of the top four under Benitez, the team didn't play well but Reina remained a force in goal, winning the fans' Player of the Season award.
Under Roy Hodgson the next season he made some terrific saves to keep Liverpool in games early on, but as the defence was asked to play deeper and not allowing the Spaniard the room to work his own penalty area, his game suffered.
From Hodgson Liverpool moved on to Kenny Dalglish temporarily then "permanently," and from then, only one year later, the King was gone and Brendan Rodgers had arrived.
Four managers, four systems of playing and four defensive methods to learn to work with in the space of 26 months have affected Reina more than most and he did not start this season in any more hopeful form.
Early-season individual mistakes blighted Liverpool's opening weeks and Reina was as culpable as anyone. Soft goals conceded against Hearts and Arsenal led to the first real criticisms of Reina, who then missed a significant period with injury sustained on international duty with Spain.
Brad Jones did his part for seven games, but though he is well-liked by supporters and seemingly by those within the club, he has never been a regular No. 1 at the top level and has not shown the kind of ability needed to help the club back to the higher echelons of the league.
There have been signs Reina was working hard to regain form.
When Liverpool played and beat Norwich City at Carrow Road, the goalkeeper was visibly frustrated with the goals the Reds conceded after he himself had made some good saves. After coming back from injury against Wigan Athletic in November Reina kept three clean sheets in four league games and the defence looked much improved from the leaky and error-prone unit of September.
Just a few weeks on though and Liverpool have now conceded five goals in their past two league matches; all were preventable goals for the defence and at least one of which Reina himself would have hoped to do better with.
The jittery performances have not helped with stopping rumours.
Safe in the knowledge that Brendan Rodgers needs to recruit heavily to shape the team to his will, the media have played up the form card to suggest that a whole range of goalkeepers are on the manager's hit list to replace Reina.
England prospect Jack Butland is another to have his name frequently mentioned in the same sentence as Liverpool these days.
Is a new goalkeeper really what Liverpool need though?
Has Reina been reduced from one of the top goalkeepers in world football and a member of the Euro 2012-winning squad just five months ago to someone not good enough for a team desperately trying to regain a place in the top half of the Premier League?
There can be no doubt that his form has dipped.
At his peak Reina displayed lightning reflexes, made top-class saves and far more importantly defended the space in front of his goal so well that he didn't need to make saves. His defenders did it for him, or he swept up through balls before shots came about from them.
Reina looks trimmer in recent weeks, presumably brought about from his altered training schedule and, in his own words on the club's website, "trying to work as hard as I could and be as professional as I could."
Whether that is an indication that he had previously let his standards slip or that he hasn't felt the gains were there to be had from working harder depends on the context the quote is taken in, but Liverpool's players in general need to be generating improved results on the pitch at present.
There was perhaps a feeling that perhaps a reunion with his old keeper coach, Xavi Valero, might work wonders for his confidence as well as his performances, but the manager has his own staff whom he wants to work with. John Achterberg remains Liverpool's first-team coach for the goalkeepers and Reina has previously indicated his happiness in working with him.
As for Rodgers, he has continually backed his goalkeeper and has given little indication (via the club's website) that he might be one of the names making way for new arrivals.
I want to make it 150 per cent clear because I've read about goalkeepers linked and him leaving. He is the No.1 'keeper for Liverpool. Yes, he will admit it himself, he probably had a difficult couple of years but he now has a sense of his best years are in front of him, not behind him.
He has lost weight, he looks fresh, he looks bright and he is doing extra work. At this very moment in time he has three years left on his contract and I think he has his best years ahead of him. I am not on the lookout for another goalkeeper and any areas we look to improve will be in other areas.
It doesn't get much more emphatic than that.
Liverpool still have a lot of work to do to ensure they get themselves back into the top six, or top four, of the Premier League, and there are certainly areas of the team which require upgrading to achieve that.
And that is certainly not restricted to the goal-scoring threat of the team alone.
The goalkeeper, though, is a position that bears a huge burden of responsibility.
Too often the casual fan might look at a goalkeeper and be enthralled by flying saves to all corners of the net. Great, but is shot-stopping not an absolute basic necessity of being a goalkeeper?
There are other, far more important factors which make a successful No. 1 and which a side who wishes to play football in the manager of Liverpool require.
For a team with a deep defensive line and strong but technically lacking central defenders who are subject to opposition getting many shots away against them, a reactionary goalkeeper might be a priority.
Liverpool though want to field a high line, pressurise further up the field and be able to utilise the space between the halfway line and their own penalty area—not just as somewhere to retreat into when they lose the ball, but as a zone to play in and tempt the opposition out of shape.
The "sweeper keeper" idea is nothing new but Reina is particularly proficient and confident with the ball at his feet, and there are not dozens of other goalkeepers around and available who might do the job as well.
Returning to organisation, Reina commands the respect of his defenders and knows where they are required to be. Being the vocal character he is, Reina directs them well, encourages and shouts when the need takes him and, when he is at his most dominant, gives the defence an assuredness and calmness.
These are not all easy traits to find in a replacement—especially in a younger and less experienced stopper.
Sure, Reina was young when he joined and he progressed to one of the best in the world for a spell—but maybe, then, that's the player Liverpool should be trying to coax back out of the woodwork rather than running to find another new player with potential to do the same.
By the end of this campaign, the 30-year-old Reina will likely have played in excess of 400 first-team games for Liverpool.
Rodgers is rebuilding the team and, it must be admitted, any parts who are not functioning to their highest level by the end of this season are likely to be jettisoned and replaced.
But Reina would be a particularly big cog to replace both on a personal and professional level within the team, and the Reds' coaching staff should be doing everything possible to help him recover his best form rather than be on the lookout for his successor.