Current 9 mm is the best choice for the vast majority of defensive uses--it is what I carry; the only exception might be in jurisdictions that have an illogical magazine capacity limit of 10 rounds or less, then some consideration might be given to going with .45 Auto. Also, if in a predominately wilderness area, .40 might be a reasonable option, although on my recent 100 mile backpacking trek through the Sierra's, I just stuck with 9 mm.