Almost finished Simon 3D, standing in front of the computer in the end after just having escaped with Swampy in the Vacuum Cleaner and now the computer asks me to enter boot disk. From guides I've read on the net it seems that I should open my real computers cd-rom station and the game will react to that, but nothing happens when I try this. I'm running the game on a Vista x64 machine.
Thanks for any help you can give me!

Thanks, as you suggested I got it working by using a cd in the drive (a truecrypt boot cd, dunno if the fact that it was a boot cd mattered, figured I'd share that info in case someone else had the issue).

Thanks for this thread :) I just got to that damn computer and didn't know what to do. I tried with a random cd and it worked :D

Thanks very much for this advice. I was really beginning to think that it wouldn't work unless i had a Simon 3D CD ROM and that would have been well disappointing.

So how would one solve this puzzle if he had no CD/DVD drive?

My question precisely. I'm currently at the very end of the game and playing on a ThinkPad with no CD/DVD ROM drive! I completed the game previously and know I'm just missing a shortish cutscene, but that would appear to be a bit of an oversight, and a shame because it's got to be one of the most original adventure-game puzzles ever created.

I think emulating it (for example with Daemon Tools) should work.
Windows 10 seems to have native DVD drive emulation.

But this riddle shows nicely why one should never make a puzzle that depends on a certain hardware peripheral or even kind of it, even if it is considered standard at that time, unless (like keyboard/mouse) it is so widesprad and necessary that it is most likely always emulated also in the future.

I created an ISO out of a random folder with WinCDEmu. I mounted it, alt+tabbed to the game, alt tabbed out, ejected it from the right-click menu, alt+tabbed to the game, and it worked. ;)