When using the MBox2 with an Apple PowerBook, "sleeping" the computer then "waking" it back up can cause this problem.

To prevent this problem, do not use the Sleep command in the Apple menu. You'll also want to go to the Apple menu and choose System Preferences. There, click the Energy Saver Panel. Set the Sleep Schedule to NEVER for both the CPU and the Screen. Aslo disable the option to put hard disks to sleep.

* It is notable that Digidesign does not support Sleep mode for any ProTools system, and that the Getting Started guide for the MBox suggests making these settings during installation/setup of your system.