You'll still need an SD card to boot from and to do the initial setup, but if you have a long-running Pi application (like my weather station project) that does frequent hdd updates and you're concerned about wearing out the SD card, you might want to convert your Pi to run from an external hard drive.
This is a nice tutorial on making a Pi run from an external hard drive:
http://raspberrypihobbyist.blogspot.com/2013/07/running-from-external-hard-drive.htmlIt took me about an hour to complete. Everything is working as expected. I had a few snags along the way, but overall it worked pretty well.
Make use that you do the apt-get update, apt-get upgrade and rpi-update steps first and that they are successful before you proceed with the rest.
Also, be sure that your external drive has its own power supply or that you power it from a powered USB hub. The Raspberry Pi can't supply an external hard drive with enough power via the USB cable alone.