You can never be safe using IE since it's being targetted the most. You must get all the latest patches and even then you're still vulnerable.
If you have a good antivirus, firewall and antispyware program, I would say that you are 99% safer already. Each has their own purpose to keeping your computer safe and although none are perfect, they will be very useful in detering most of these infections.
rantsh, the antispyware program that Microsoft has is Microsoft AntiSpyware. I don't recommend users to use this program anymore as they seem to made an agreement with a spyware/adware company. Now instead of setting those spyware/adware related files to remove/delete, it's set to Ignore in the Microsoft AntiSpyware program...which is not what we want since we want them gone. Install and run it if you wish, but I say use Ad-aware and Spybot since those two will basically catch most of the known ones out there.

