Sometimes the application will have drivers that need to be recompiled after a kernel upgrade, but other than that I've never had an issue. I usually will take the downtime and upgrade, but lately I haven't had the time. My server has been up for about 8 months now, and I probably won't bring it down for upgrades until Zimbra 6.0 is final and I do my Zimbra upgrade. I'll upgrade the kernel at that time.
Release 6.0.2_GA_1912.UBUNTU8_64 UBUNTU8_64 NETWORK edition + Mobile Option
Activesync with Moto Q9C, HTC Touch Pro, Palm Pro, & Palm Pre