I use Skype. A lot. Not only do I use it as my office phone, but I use it to record remote callers for podcasts, so the quality needs to be really good. The best way to accomplish this is usually with a good USB headset.
I've gone through more USB headsets than I care to think about mostly due to the lack of comfort but also due to obsolescence - they just die out after awhile.
A year or so ago, I bought a pair of Shure SE110 headphones for my iPod and I love them.
When my current USB headset suddenly died, I had an immediate need for a headset for a series of conference calls. I've got half a dozen Griffin mics laying around so this is what I came up with.
Using the USB dongle from another pair of headphones, I plugged my SE110's into the headphone jack and the Griffin mic into the microphone jack and voila - great, portable setup.
Geek Note: the USB dongle acts as a analog-to-digital converter for the audio-into your computer and a digital-to-analog converter for the audio-out of your computer. Your computer probably has a sound card that can accomplish this but a USB dongle is basically a device dedicated to this purpose and usually provides better performance.
This setup sounds great and I can wear the headphones for hours in comfort. As for the microphone, Griffin stopped making them but you can find them on eBay, usually new and in their original packaging.