Between them, that elite quartet has scooped up 31 of the last 32 Grand Slam singles crowns, with Del Potro's breakthrough victory at the 2009 US Open the sole exception.
"It's really tough, those four guys are making history in every Grand Slam and every big tournament they play," Del Potro told Reuters at the BNP Paribas Open being played at the Indian Wells Tennis Garden where he has reached the quarter-finals.
"Me, and a few others like (Tomas) Berdych, (Jo-Wilfried) Tsonga and (David) Ferrer are trying to get into that big group but it's not easy. They are playing so well and you can see in almost every Grand Slam the top four are in the semi-finals.
"It's not easy beating them in a Grand Slam. You have to be 100 percent that day and then see if they don't serve like you, if they give to you a little opportunity to beat them. I made it in 2009, then I got the injury with my wrist."
Following his stunning five-set triumph over Federer in the 2009 US Open final, Del Potro had been expected to cement a place close to the pinnacle of the game but his burgeoning career was swiftly derailed.
In 2010, the towering Argentine played only three tournaments because of an injury to his right wrist which required surgery and he ended up being sidelined for eight frustrating months while recovering.
"It was tough," said Del Potro, who will face world number three Andy Murray in the last eight at Indian Wells on Friday.
"When I came back to play tennis I wasn't seeded in any tournament.
"I remember I came here and in the first round I played (Ivan) Ljubicic, after he made the final the previous year. Then in Memphis I played (John) Isner in the first round. Those were not good moments for me."
Del Potro said it took him an entire year after his return to the ATP circuit before he felt completely healthy.
"I needed all that time to be confident with my wrist and to get up every morning thinking about my tennis game and not about my wrist," he said. "It takes all the year to be ready mentally again."
Asked how much his 2009 US Open win had boosted his self-belief, Del Potro replied: "Well, I knew that I had done it and it meant a lot for me.
"I made my big dream but now, for this year, I have a big challenge trying to do something similar like years before. Last year I was close at the French Open when I was two sets up against Federer in the quarter-finals but I lost.
"Then I make another quarter-final at the US Open but lost to Djokovic in a big match. I broke that run at the London Olympics when I got the bronze medal but it's not easy. We need to be 100 per cent for two weeks (to win a Grand Slam title)."
Last year, the 6ft-6in Del Potro triumphed four times on the ATP World Tour after reaching five finals and he has already added another title this season in Rotterdam.
"I always raise my goals and I am trying to do a good schedule for my game this year," said the 24-year-old from Tandil. "I already won in Rotterdam, a big tournament, and then I made the semis in Dubai.
"And now I am here at Indian Wells trying to go far, play at my best level and then see if I have the chance to win this tournament. I have been playing at a good level and I like this tournament.
"But I know that to be with the top guys, you need to do get good results in the 1000 Masters events and the Grand Slams."
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