According to Guy Kawasaki there are three types of computer users:

1. who backup
2. who learn to backup after a HD-crash
3. who think their HD is never gonna crash again

This article is for person in category 1 and 2. I really can’t help you if you belong to number 3 ;-)
If you work in a company and don’t have to take care of your data, good for your, but still, what do you do with your data back home?

My basic tips are:

1. Do backup
2. Make sure your backups actually work
3. (Bonus) Don’t keep all data in the same place

Pretty easy, isn’t it?

As a minimum: use Apple’s TimeMachine!

As always in this blog: I do what I preach, al those tips and ideas are what I do and have been doing for years to keep my data safe. The technique was originally developed long before there was Mac OS X 10.5 and TimeMachine and while TM might do the trick for many people you might find some tips here for your own backup workflow. My desktop setup also contained a RAID0 set for speed reasons which meant twice the chance of data loss. As it was a productive system, even when this happened, i wanted to be able to get right back to working within minutes.

So part 1 of my strategy was a identical clone of my hard-disk. Automatically done every morning every morning right before I show up for work. I know there are free tools out there for that, but for over 5 years I have been using SuperDuper and it hasn’t failed me once. I did so many clones, backups and restores that I can fully recommend it to all my friends.
The great thing about a backup in the morning is, if I have an epiphany in the night that I actually wrecked something I was working on that day, I just show up 20 minutes earlier and copy it back before the backup starts. :)
If I install any new software, be it an Adobe update or a Mac OS X update, I always first make an full clone and keep that for 1 or 2 weeks, you never know what problem you might run into while working, even if the update installs fine. (And if you install an update on the day of its release, you can’t be helped either ;-) ).
If you haven’t done this before, I highly recommend after your first successful clone, to make sure, that you can actually boot from it. Turn your mac off and right after turning it back on, hold down the “alt”-key and the bootmanager should show you not only your internal disk, but also the newly created clone. Select it and test if your Mac boots.
You can also just do regular (weekly, monthly) backups and use TimeMachine for continuos backups of your files.
Especially for mobile Macs, but also for the case of burglary or a fire: make sure to have your data not just in one place. If someone breaks in an takes your Mac and your externals discs, a backup isn’t worth anything if it’s gone, too. So for example put a external disk in your sock drawer (good against a fast break-in) or drop it off at your parents place which pretty well protects you against “elementary damages” as insurances like to call it. You don’t even need an external enclosure for your backup HD. Instead I just use an USB to SATA adapter (around 30 bucks) I connect my drives to and then put them back into their packaging. To recover more quickly _if_ something happens I normally have a partition on my backup-disk that contains a clone of my Mac OS X install DVD, the latest updates of Mac OS X and installers of my software. This way, even if I should experience a full crash while on the road I have anything I could possibly need with me. (Also great, if you have a flakey DVD-drive)
Then there is also the internet for backups. Services like Backblaze enable you to store your data somewhere far, far away in a datacenter, even with your own encryption-key. While with most connections the initial backup takes ages, why not use the available bandwidth at night? Of course it’s not necessary to backup your full disk to such a service. A System can be reinstalled, installer DVDs are lying around somewhere and music can be re-ripped or could even be re-bought, but your pictures, home-movies and project data is lost shouldn’t you have a backup somewhere. Just make sure for yourself how much that personal stuff is worth to you.

So, to sum it up:

Clone your HD regularly, clone it before updates, make sure backups work, but backups offsite.