I hope this isn't a dumb question...

I have a 27 gig hard drive with only MAME on it. I have just added a 120 gig hard drive and am about to put about 70 gigs worth of console emulation on it.
I am wondering, if I use a FE (like DK or MameWah) do I need to have all the Roms/Emulators in the same folder? Or will the FE work with them being on two separate hard drives?
Thanks in advance,
Sshado