WARNING: The following contains spoilers for Chapter #304 of My Hero Academia by Kohei Horikoshi, Caleb Cook and John Hunt, available in English via Viz Media.
For multiple reasons, the amazing Quirk known as One For All has always been a standout in My Hero Academia. To begin with, this Quirk is what allows its powerhouse user to execute devastating Smash attacks, from Texas Smash to the mighty United States of Smash. One For All once belonged to All Might himself, but there's more to it than that.
Unlike most other Quirks, One For All can be voluntarily passed from one person to another. Nana Shimura (the seventh user) passed it to a young Toshinori Yagi (All Might) who in turn handed it over to Izuku Midoriya. One For All is a real boon for a naturally Quirkless person like Izuku, but recent manga chapters have shown that Quirklessness might even be the vital key to using it correctly.
The Strain Of Wielding One For All
For months, Izuku has been seeing strange silhouettes of One For All's previous users. The first instance of this occurred during the U.A. sports festival, when Izuku nearly lost at the hands of Hitoshi Shinso's brainwashing ability. Now Izuku is properly meeting OFA's previous users, and they have some vital secrets to share. For one thing, most of the previous users died young and in battle, not living past age 40. Clearly they were under a lot of strain, but One For All alone wasn't the problem. The real issue is that these previous users were born with their own Quirks.
It is possible for someone to have more than one Quirk. There's the powerhouse villain Nines and All For One himself, who wields hundreds of them. What is more, All Might once considered giving One For All to Mirio Togata, who was born with the Permeation Quirk. But had he gone through with that, he would have doomed Mirio to a short life. One For All, as it turns out, wears out the user's body if it has to share space with another Quirk factor, and that is why its previous users all died young. The human body can't easily handle having two Quirks at once like that, especially when one of them is the powerhouse One For All.
As an example, One For All's fourth user Hikage Shinomori was born with the Danger Sense Quirk, then he received One For All. He died early due to the strain but did hang on to One For All for 18 years -- longer than most other wielders. Hikage spent all that time training in seclusion, simply building up One For All's power so a future wielder could use it to finally destroy All For One in battle. Likewise Nana Shimura, who had been born with the Float Quirk before receiving OFA. But then there's the matter of All Might and Izuku, who both avoid this problem entirely with their Quirkless nature. Being born with zero Quirks has its upside after all.
An Empty Vessel, Ready For Power
Most One For All wielders had their own natural Quirks, but that changed when Toshinori Yagi received it from Nana Shimura and began to call himself All Might. Without a Quirk factor, a wielder must have a strong physical body for One For All, and a generation later, Izuku Midoriya began the same path. Thus, they were both ideal vessels for One For All.
Izuku and All Might had more "room" in their bodies for One For All, which wouldn't clash with an existing Quirk factor. This prevented undue strain on their bodies and freed them from the fate of dying young. All Might fought with this Quirk for nearly 40 years, something the previous wielders could never hope to achieve. He served as a heroic symbol of peace and hope with this power before passing it on to Izuku, who is essentially All Might 2.0.
But there is one catch. Quirkless individuals were fairly rare to begin with, and now they are practically gone. Essentially everyone is now born with a Quirk, and that means trouble for One For All. It may soon become impossible to find another Quirkless person who can safely use OFA the way Izuku and All Might do, so previous users conclude that Izuku may be its last proper wielder. The stage has been set -- now it's up to Izuku, the ninth wielder, to finish the job and destroy All For One, Tomura Shigaraki and the League of Villains with his incredible gift.