I am required to run skype (yuk) for work, and, since I am rather paranoid, I had up to now been running it under a separate user account (so it's long history of security problems would not endanger me too much). This was a bit inconvenient, though; it meant that I had to start it manually instead of the desktop session manager starting it for me, for instance.
I was intrigued by the AppArmor support in the latest version of Ubuntu, however (Ubuntu AppArmor), and decided to try that instead. I took a sample apparmor file suggested by SuSE and updated it to work on x86_64 and Ubuntu 9.10.
AppArmor profile for skype 2.1.x on Ubuntu 9.10 is here. Note that this is a very conservative profile ‒ it prevents reading or writing to your own homedir (hopefully preventing malware or skype exploits reading your ssh keys, private files, etc) other than ~/.skype and config files that it needs from other areas. Your abstractions/audio needs to be correct for audio to work. It specifically prevents opening URLs by clicking on them (protection against spammed malware links) ‒ you have to copy and paste to a browser. If you think the inconvenience outweighs the safety gain, this patch is not for you :-).
No warranty. Importantly, this can't protect you against the poor security of the X window system itself; skype exploits could still do keylogging, for example (unfortunately skype refuses to work with x.org's security extension enabled for it, as do so many programs; indeed, skype 2.1.x it itself now using the evil are-you-typing monitoring that is now a staple feature for malware, so you probably can't distinguish from its normal behaviour).