So im sure you've seen this question before, would a .22 LR pistol be good for HD. I realize its not a first choice, but in my mind, a well placed shot will do the same as a .45.
It can be effective against human targets, in my opinion, but because of its relatively small size, low power, and other issues that have already been brought up in this thread, it would be of great benefit to very carefully select the right combination of quality ammunition and firearm (mostly with regard to barrel length) that will likely achieve effective terminal ballistics.
First let me address the issue of stopping power--except perhaps for the most powerful centerfire rifles, there is no such thing unless you hit the right spots, namely the CNS or major cardiovascular structures. So it's really all about shot placement, just like most everybody says these days.
Now let me address how people view shot placement. Some people at least seem to think or imply that in a real shooting you can so precisely place shots that a slightly larger bullet (even a .45 ACP bullet is only slightly larger than a .22 LR bullet--it may be about twice as wide, but twice of tiny is still tiny in comparison to the body) will give you some margin, but in my opinion that doesn't have much validity. Unless the bad guy is just standing still begging to be shot, you may need luck to hit him at all, and luck is exactly what will determine exactly where you hit him and whether that shot will be effective. In fact, luck ultimately determines the outcome of everything in life, and all we can do is affect the probability. Larger bullets will improve your chances in this game of luck, but only by a little bit, not the huge difference that many wish to believe (as I once did).
However, one thing that you do need in order to have any chance in the first place is sufficient penetration, which is often iffy with .22 LR. This is what depends the most heavily on the combination of ammunition load and firearm. Sometimes more powerful/faster loads will penetrate more, but sometimes the opposite is true. What I want to stress, though, is that .22 LR can indeed achieve sufficient penetration to be effective--just as much penetration as a typical defensive JHP load in a larger handgun caliber, or even more if you like.
Let's look at some examples before continuing. The CCI Stinger, a favorite among many because of its extremely high velocity and energy for .22 LR, is actually not that useful against humans. The hollow-point bullet is light and weakly constructed, and when shot out of a rifle will literally explode into fragments at a shallow depth, which while spectacularly devastating against squirrels and such, is not very effective against larger creatures. Shot out of a handgun with a medium-length barrel, the bullet may actually expand as designed, which limits penetration severely in this caliber, thereby limiting its overall effectiveness. Only in snub-nosed revolvers (and various derringers) does this load shine against human targets, penetrating enough to be effective by most standards (because it does not expand in this case). The CCI Velocitor, on the other hand, works well out of both medium-length handguns and rifles, achieving sufficient penetration in both and expanding in the latter to improve your odds a little bit; out of snub-nosed revolvers, I imagine that penetration would be somewhat lacking, however. There are many other examples to consider, and a few lab tests to verify some of them, but the point is that there are ammo/firearm combinations in .22 LR that are effective for defensive purposes, as long as you're careful in choosing.
Another issue to address is reliability. Frankly, I wouldn't trust semiautomatic handguns in .22 LR, but revolvers and many rifles are fine. One issue with rimfire ammunition in general is its well known lack of reliability in ignition, but that's only true for cheap bulk ammunition. Quality rimfire ammunition from CCI, Aguila's specialty loads, and Eley match loads, for example, have been about as reliable as centerfire ammunition, in my experience.
And finally (as if!
), I'd like to stress the importance of how well one can shoot a certain caliber over its physical attributes. Although some calibers are certainly more effective than others, even .22 LR can be nearly as effective as any, so this is nowhere near as important as being able to accurately place a quick succession of shots into a target. There is simply no better way of maximizing your chances of a successful stop through shot placement than placing lots of shots!
Regarding handguns, some people can shoot .45 ACP or .40 S&W both quickly and accurately, so I wouldn't blame them for using those calibers at all, but some people (especially beginners) can shoot .22 LR a whole lot better than they could larger calibers, so it may well be advantageous overall for them to shoot .22 LR (as hard as that might be for them to admit).