We look back at cases ranging from Liam Brady to Stephen Carr
After the career he has had and the impact he could still have as a substitute, it would be sad to see Robbie Keane miss out on Euro 2016.
A calf injury has led to worries that the LA Galaxy striker, who played at World Cup 2002 and Euro 2012, could miss out entirely as Ireland prepare for a final friendly against Belarus in Cork tonight.
Fingers crossed the captain makes it, but he wouldn't be the first Ireland player to face the disappointment of missing a major tournament.
Before Euro 88, we never managed to make it to a major tournament and by the time that European Championship came around, Liam Brady was coming towards the end of a brilliant career.
Euro 88 would have been a great opportunity to show his talents at international level, having done so for Juventus and Arsenal on the club scene.
But unfortunately, the midfielder was robbed of that opportunity in '88 due to a combination of suspension and injury.
He had played in every game of the Euro '88 qualifying campaign, scoring a vital late equaliser in the group opener against Belgium, but a cruciate knee ligament injury hampered him, as did a two-match suspension for lashing out at a Bulgarian player in the final qualifying group game.
Brady was never a true favourite of Jack Charlton, in any case, given the latter favoured a direct style of play not especially suited to Brady's approach and unfortunately, the Arsenal and Juve great was missing for Italia 90 as well.
Lawro was also unavailable for Euro 88 as the former Liverpool defender was sidelined by injury.
He was the scorer of a crucial winning goal away against Scotland in the qualifiers which went a long way in taking us to the finals in Germany.
An Achilles injury was the root cause of his absence from Ireland's first ever major tournament.
Mark Lawrenson ©INPHO/Billy Stickland
A flying right-back for Tottenham Hotspur at the peak of his career, Carr would have been a likely member of the 2002 World Cup squad.
A knee injury would later end his career years later, but it was the same body part which cost him his place in Korea and Japan.
It was a long-standing knee injury which not only hampered his 2001-02 campaign but also robbed him of a World Cup chance at a time when he was one of the more highly-rated full-backs in the Premier League.
"The World Cup's gone and it's now about getting myself fit and playing football again. I knew my season more or less had gone at Tottenham so I just wanted to get fit, play a couple of games and get into the World Cup squad but it's not to be for me this time," he said after visiting renowned American knee specialist Dr Richard Steadman.
"For the last six weeks it's been hard. One minute I think I'm going to the World Cup, the next I don't and I've been up and down like a yo-yo. But it's not to be and I know where I stand now."
Doherty was a regular squad member either side of the 2002 World Cup but unfortunately the effects of injury.
He recently spoke to Newstalk's Team 33 about the disappointment of missing out, having broken his leg in a League Cup match for Tottenham in the Autumn of 2001.
"I snapped my leg. I broke my ankle but I didn't realise the breaking of the ankle was going to be the thing that would take so long," he told us in March.
"That was the thing that really took time. It took eight months to get over the ankle injury. I remember we played America in Lansdowne Road [in April 2002] and I scored and I thought maybe I've got half a chance of making the squad now because I could play two positions. I thought that might weigh in my favour but there were other lads who had been playing in the Premier League all season so looking back there was no way I was ever going to take their place. But yeah, it's one of my big regrets especially missing out on a World Cup."