For many years I've been backing up my various computers to external USB drives. Since becoming a Mac convert I've switched from rsync to Time Machine and never looked back.
jwz's most excellent backups article is what really gave me a kick in the pants to back up all the time. And having a backup has saved my bacon on more than one occasion.
The only thing missing from this equation was my "house burned down" backup.
That third drive? Do a backup onto it the same way, then take that to your office and lock it in a desk. Every few months, bring it home, do a backup, and immediately take it away again. This is your "my house burned down" backup.
Yeah that. That I have never had. So I've decided to fix it.
Now I backup everything online to Backblaze. For $5 a month, it's a no brainer really. So far it's never gotten in my way, has backed up everything and restored what I needed it to in testing.
Even though everything is encrypted, I did have a brief moment of "oh noes, all my stuffs are on teh internets". So I added my own encryption key into the mix as well.