Carrying or using a handgun for self-defense is a time-honored and Constitutionally protected right in this country. What you carry is also, as many other things in life are, totally up to you. While many argue that the minimum amount of gun to carry to protect themselves is in a caliber that "starts with a 4" there are also some inside the same community that go about half that size and carry... 22's for self-defense.
Come on, why a .22?
First, let's look at this objectively. Some of the most accurate, inexpensive, and reliable handguns of all time are rimfire pistols and revolvers. A good used Ruger Standard or MkII can be bought for around $250, .It is almost impossible to break, accurate at the day is long, and 500 shots of practice run about $15. More modern versions of this handgun by other manufacturers, such as the Beretta Neo, Walther P22, and Browning Buckmark run slightly more but are no less dependable if using the right ammunition. For the same price, you are looking at buying a Kahr or Kel-tec pistol in 380/9mm. At the range 500 rounds of .380 is about $175, or about 11-times more than the same amount of .22LR rounds. This leads to more bang for the buck in the most literal sense, allowing both more frequent and more intensive training and practice.
Furthermore, most .380s have a pretty good bark and resulting muzzle-flip that many shooters find uncomfortable and makes for slower aimed follow-up shots. Furthermore, if you need a very small handgun, there are no smaller than the Beretta 21 subcompact, NAA Mini-revolvers, and two barreled derringers made by several manufacturers-- and all are rimfire 22s.
Bonus Add Ons
Besides being a home defense or personal defense firearm, .22's are the penultimate target handgun for tin can plinking at the local gravel pit, and punching holes in paper at the range. Many states allow handgun hunting and the .22 handgun is a proven survival tool for rabbits, squirrel, and other critters. I know of one older Southern gentleman who very successfully hunts deer with a long barreled AMT .22 Automag pistol. That's a lot of multi-tasking for one handgun. With today's lean economic times, you may just be able to have one to cover target shooting, home/self-defense, and hunting.
Can a .22 be lethal? With thousands of people on both sides of the spectrum dead and buried over the years by rimfire rounds, you had better believe it. Is it a good choice for personal defense? It can be argued that almost every round that is larger than a rimfire .22 penetrates deeper and imparts more energy onto its target. It's a matter of simple physics. If you hit something with a 230-grain bullet going at 800 feet per second, it's going to cause more damage than if you hit something with a 40-grain bullet going at 1000 feet per second. The FBI recommends to law enforcement that a round penetrate 9-inches of more in ballistics gel to be considered 'combat effective.' In tests from a Taurus subcompact pistol by Golden Loki, no less than eight loadings of 22LR met or exceeded that benchmark.
See below gun test for a 22LR CCI Velocitor through a chicken and four layers of terry cloth.
When you talk .22WMR, the figures change up the board slightly. Manufacturers are even catering to personal protection ammunition for these chamberings. Hornady's Critical Defense Ammunition is loaded with a 45-grain Flex Tip Expanding bullet, which has a soft polymer insert that delivers superior controlled expansion and large, deep wound cavities over a wide range of velocities. Each round is loaded into a nickel case for increased visibility in low-light situations and premium low flash propellants that deliver proven performance, even in very short-barreled handguns that will not disrupt your vision.
They generate 100-ft/lbs of energy from a 2-inch barrel. Not an elephant gun by any means, but still more effective than bad breath and colorful language. Ballistically speaking the 22 in either LR or WMR flavors is capable of self-defense, but only just that.
Minuses of a 22
While a 22 may be lethal, it is still just 33-60 grains of bullet traveling at pretty low speed. They are well known for ricochet against hard flat objects, as any squirrel hunter shooting up into an oak tree will tell you. A .22LR can even ricochet off the surface of water at a low angle of aim. Bulk pack plain Jane rimfire rounds are cheap, but many of the better rimfire rounds like CCI Stingers for example, cost around $7 for 50-rounds. This is a price approaching that of bargain 9mm or .38SPL that would hit a heck of a lot harder by comparison.
Overall, while it's generally recommended that you bring enough gun to the fight, by carrying the largest caliber handgun holding as many rounds as you can get away with that you are comfortable toting around, for some this choice is a 22. It's better than nothing, especially when the alternative is an empty hand.
Be safe out there.