Skype

What exactly is it that you want to do here?

It's very hard to answer your question without knowing what you want to achieve.

Col

Don't allow people to be administrators, so that you can control what gets installed on the boxes...

or take the code of some malware rootkit that would scan for and terminate AV processes. Add Skype to the target list, next, prepare your resignation letter, just in case... :)

On a more serious note:
What do you want to do?

If you are the network administrator of a domain, then you'd simply not allow your users to install things that shouldn't be there.

Instead, or in addition, you could try to block skype traffic. Google for "how to block skype network traffic" to find more on that.

Or, are you rather trying to stop some family member from running software that you have installed for your own use on a shared computer?

See. Tell us a little bit more, and you may even get useful answers...

You can effectively block skype from being downloaded and installed by creating a local zone for skype.com on your internal DNS server, pointing to a fictional IP address like 127.0.0.1 or 0.0.0.0 This will also prevent already installed versions of skype from being able to login.

A better solution might be to use http://www.dnsredirector.com to block skype.com and other IM/video/chat clients, with the option to have some users bypass the restriction by entering a code (or having someone from IT come over and enter a code)