It's a DOS game so go with DOSBox. While installing, it went like most games.

These are the DOSBox settings I prefer.
output=ddraw
memsize=63
joysticktype=none
Everything else at default.

Select Digital
Sound Blaster 16 220 1 7

Select Midi
Sound Blaster 16 388

CD-ROM is required to play as most of the game resource are located there.

[Moved to DOSBox Games/Apps. Section]

Your best bet is to use DOSBox for this game.

Okay, so DOSBox is the best bet? How do I get it to work in DOSBox? I tried mounting an area to use as my C: drive, and that works, but I can't get the CD to load (tried mounting direct from CD and was told that CD drive doesn't exist, and from files copied to hard-drive then mounted as if it were a CD - which gave me an error message (I don't have it open right now so can't check) but still wouldn't let me run the game.

SKARDAVNELNATE, I understand that you've had success with making it work? I'll look to see if I can use those settings - are you able to give a bit more info about the steps that you used to get it working?

If you have the CD in optical drive D:\
MOUNT D D:\ -t cdrom

If you made an image of the disc named Millennia.iso and store it at C:\DOS
IMGMOUNT D C:\DOS\MILLENNIA.iso -t iso

Once mounted switch to D:\ and type install

Read this guide and the readme file that installs with DOSBox for more details.

I've done that and it gave me the message:

D:\>install
Millennia CD-ROM v1.0
Installation Program v2.1
Copyright (C) 1994-1995 Take 2 Interactive Software

This program will copy several files that will be used to get the rest
of the game running. THey require about 5120K of hard disk space.
Additional space will be required for saved games.

Run the CD installation from the CD-ROM drive.

Which I guess means I'm heading in the right direction. Still can't get the game itself to run though. Repeating install gives me exactly the same message.

When trying other files from the disc I get the following:

Searching For CD-ROM...
MSCDEX not loaded.

Except for _setup, which runs the setup file. And ECGAME which goes to a blank screen with "Ex:5096h" on it.

MSCDEX not loaded.

Did you use the -t switch?
-t cdrom or -t iso have to be lower case.

Still can't get the game itself to run though

Start the game with C:\MILLENIA\MIL.BAT after installation.

Thank you! I spent most of yesterday playing the game - and for the first time ever I'm also able to see the video segments that go with it. Not bad after 15 years!

Now all I need to do is figure out how to get three species to advance and I'll be able to complete the game (the sloths seem easy, the others are not so willing to advance).

Advancing them I got. Getting them to balance out after has been impossible so far. Keep notes, we can compare later.