Best Strategy For Updating Lists

Hello,

Probably been asked many times, but in searching I don't see it, so . . .

I have three lists that come out of a National Database.  Each represents different members of an organization.  We ned to keep the lists separate as there are requirements to send to just one of the lists sometimes.  The lists are updated on a semi-regular basis as new members to the organization get added, or fall off.  I'd like to be able to just REPLACE the entire list(s) for each membership as they get updated (they come to me in Excel), will this update the contact list correctly, or am I looking at the list update process incorrectly?  Thanks in advance to all.