It's not so much that it's one file (although that makes for fun times if the underlying filesystem doesn't support proper write locks), after all most databases also use just one file -- it's more the fact that individual messages are only recognized by lines starting with "From: " -- which presents some obvious challenges with escaping (that some programs manage to get wrong). I also imagine it'd be challenging to maintain an effective index as mails are deleted...

Well, there are MTAs, which one may use to distribute mail to different mailboxes. Also, no one is obliged to not truncate their mbox files after a while. I just encrypt my set of files and tuck them in a tarball, and store that in a specific folder with older tarballs.