The biggest caliber an American civilian shooter can easily get is .50 BMG. This is the round that .50 Browning machine guns use.
There are bigger calibers out there. Some elephant rifles use cartridges that fire a .60 caliber bullet. If you have the right paperwork and permits from the federal government, you can buy a small cannon and shoot 30mm or larger rounds. But among "common" rifle and pistol calibers, the .50 BMG is king of the hill.
.45 Caliber is the largest caliber Glocks chamber.
50 caliber
You will haver to define if "biggest" means caliber or overall size.
.17 to 20x110 Hispano
.500s&w
In guns including firearms, caliber or calibre is the approximate diameter of the barrel and by extension the projectile used in it, measured in inches or millimetres. The 20mm caliber ammo is the biggest one in production.
The .950 JDJ is the biggest rifle The biggest hand held gun is the 600 Nitro Express Pistol
It depends on whether you mean legally, or what is the biggest handgun available, and whether you mean handgun size, or caliber size. The largest commonly available caliber is .45 ACP, however, .50 AE is also fairly common. That said though, there is also a handgun available in .600 NE. Most states don't have restrictions on caliber, however, some may.
There has been a revolver made in caliber .600 Nitro Express. This was an elephant rifle cartridge. As a firearm, it is a curiosity, and not a practical shooting firearm. There are also unconfirmed reports of a Maadi bolt action pistol in caliber .50 BMG.
The BATFE web site has information that can assist you in answering your question.
Largest standard caliber is likely the S&W .500 Magnum, but revolvers HAVE been built in .600 Nitro Express.
Caliber refers to the diameter of the bullet. A 50 caliber bullet is .50 of an inch (half an inch) in diameter. It's also used to refer to a gun that shoots a 50 caliber bullet. The problem with the word "caliber" is that it has two different and confusing meanings. In small arms, "caliber" usually refers to the diameter of the bullet, NOT the casing, and is measured in inches (i.e. .50 caliber is 50/100ths of an inch, or a half-inch). [Note: your original question should be ".50" caliber, not "50" caliber.] The biggest problem with this usage is that it's not exact - the most common .50 caliber bullet (the .50 BMG of the Browning .50-caliber Heavy Machinegun) is actually .510 inches at the widest point. The other use of the word caliber is the ratio of the barrel bore (inside) diameter to its length. For instance, the huge 16" guns on the US's Iowa-class battleships are properly classified as 16"/50-caliber guns, which means that the barrel length is 15 times the bore length; thus, the 16/50 is 800 inches long (66 feet, 8 inches). While this usage of caliber is most common for cannon (and not small arms), it nonetheless can be found in discussions of rifles.