Recent case of the 92 year old vet that put down a punk with a .22: Earl Jones Shoots and Kills Suspected Robber at Kentucky Home | Video | TheBlaze.com
Anecdotal, yes. But the punk is dead.
Bottom line - if you can handle a larger caliber, you should. But if you can't, then a .22 handgun can certainly do the job.
It may also depend on the situation as well - I wonder what would be more effective for home defense - a 10/22 carbine with a 25 round magazines or a .357 with 7 shots?? It's a lot easier to hit your mark with a short rifle. I'd still reach for the .357, but I wouldn't feel undergunned with 25 rounds of .22 hollowpoints.