I posted the original question on the sustainability thread because my question is only in part about "effectiveness." Survival questions focus on "use" and tend to drift into "caliber" discussions, with the arguments breaking down into themes of "you need at least this big of a caliber to survive a [insert] attack." While that's interesting, the point is consistently made that no single "caliber" can cover it all in "survival". But I didn't ask about "caliber", I asked about "handgun," and I asked it in the "sustainable living" thread.
Sustainable living implies self-sufficiency for the long term, and in a bad-case scenario, perhaps for multiple generations. Whether its triggered by a major event for which many folks will slip into a "survivor" mentality, or the sustatinable lifestyle becomes a necessity as the economy continues to dip, the bottom line is: you cannot rely on anyone or anything over and above what you have prepared, for anything you require. In that frame of mind (i.e. sustainable living), if you could only have one handgun, which one would it be? Unlike perhaps others, I expect a handgun to be like underwear or a good pocket knife - on me all the time.
For example, it could be a Smith & Wesson Double Action Revolver in .357, maybe stainless, with a couple of sets of grips. You may have picked it because you've found it to be a durable, simple to operate and simple to maintain action that you fully anticipate will continue to serve your grandchildren when you are long dead. You may have picked it because you know that everyone in your family can operate it; you can use it in either hand if you're injured. In order to sustain that handgun, you probably have the means to cast bullets and reload for it. It would require stockpiling powder and primers, and nothing in the support chain should require electricity. You might have holsters for it, and cleaning gear. You may have chosen that caliber for the uses you expect, like hunting pig and deer, and killing predatory animals, within your practiced limits, or self-defense against a 2 legged predator. You may have a different sustainable option, like traps or snares, for getting small game, so a .22 might not be as necessary for you. You may have a different sustainable option for large game, like a selfbow with your own arrows, so a centerfire rifle might not be as useful to you for that role.
Or you may not feel comfortable unless you have a collection of firearms like golfclubs - a different specialized tool for every job in your sustainable lifestyle. In which case you would naturally have to cover multiple calibers, various tools, parts, etc. Its a much more complex sustainment issue, one the military, for example, avoids because of cost and complexity. But if you have the means, go for it.
I left defense against raiders, zombies and grizzlies out of my equation as they are so unique as to require their own solution, if they cannot be avoided ... which is the most sustainable option.