I've said in a couple of places that my biggest problem with Colemak is that it just doesn't suit me on a flat keyboard, such as my laptop. However, having said that, I find it works very well with a split ergonomic keyboard such as my Microsoft Natural 4000.
The reason for this is that when you're using a layout that is tightly optimised to the home row, it forces your wrists together into a more awkward angle than if you were naturally resting your fingertips on, say, the keys QWEF / JIOP (QWERTY) or QWFT/NUY; (Colemak). This is why I don't use Colemak on my laptop -- it got just too uncomfortable after an extended period of use.
I've seen one or two other suggested answers to the problem, e.g. DreymaR's bottom row shift, but I'm not entirely convinced that that's the best we can do for comfort even yet. However, I was wondering, what would a keyboard layout look like if we were to abandon the sacred cow of the home row and instead optimise for the alternative home keys that I've suggested? Based on Colemak, something like this would probably be your starting point:
* * * * * * * * * *
A R S * * * * E I O
* * * T * * N * * *
* * D * * * H * * *
If you optimise for this kind of arrangement, it would allow your wrists to adopt a more natural and comfortable angle on a conventional keyboard.
Is there any mileage in this idea? What if we moved the home keys down a row to ASDVMKL; / ARSVMEIO ? Any other suggestions?