I use Skype for telephone serv ice in my office.  By leveraging the Skype Out and Skype In functionality, clients can call a normal land line phone number and reach me regardless of which computer I may be on.  Even when I'm traveling with my laptop, I can receive an place calls.  My only equipment I need to have with me besides the laptop is a headset. 

I have discovered one custom setting that I make after starting Skype.  It involves boosting the process priority of Skype.exe and skypePM.exe.  I set the priority to Above Normal using the Windows Task Manager.  Effectively this gives Skype precedence over my other processes which may include mulitple VMWare virtual machines (all of my development is done using Windows 2003 Server VMs).

After boosting the priority, I'm having near perfect conversations now with very little static and sound break up.

To change the priority of the Skype processes, follow these steps:

1.  Start Skype.

2.  Start the Task Manager by pressing Ctrl-Shift-Escape.

3.  Click on the Processes tab.

4.  Click on the Image Name column to sort the column.

5.  Scroll down and located Skype.exe and skypePM.exe.

6.  Right click on each Skype.exe, choose Set Priority, and click Above Normal.

7.  Repeat step 6 for skypePM.exe.

I've tested these steps successfully on Vista Ultimate 32 bit and Vista Ultimate 64 bit using Skype Version 3.6.0.248. 

Let me know if you have better Skype success after making these changes.