If you mean internally:
The manual doesn't specify what size drive it supports that i can find. however, the OS would likely be your biggest culprit of issues. if you're looking to use a single 3TB drive to store data you rarely retrieve, you will be ok. if you're looking to stream DVD or better quality movies, that large of a drive with the table size it will create for that much space you'll have performance issues with the OS being slow to respond while it's scanning all the platters for the data to bring to you for the movie, while still running the OS and any other apps you're running in the background.
If you mean Externally:
Yes, I have a 3TB and 2TB connected to mine now. these are my redundant backups of my docs, music and applications that i want to save.