Make your hotel/motel/campground reservations. Make sure to allow adequate time when mapping your trip so that you can arrive at your hotel around dinner time. Any earlier and you're wasting opportunities to check out sights along the road, and if it's later, you'll be exhausted! Call the office of your accommodations to let them know your ETA if it will be later than 5:00 pm.
Print out all of your hotel/motel/campground reservation information as well as any other reservations you have made (or tickets purchased) and keep these with your maps. I recommend that you designate a bag for these things (preferably waterproof) where they are always kept and, therefore, less likely to be lost.
Get an oil change and have your car checked out (including the tires). Get any repairs needed done now! Make sure your spare tire is in excellent shape and you have a jack/etc. to change it. Also, spring for a road-side emergency kit with flares, jumper cables, and the works.
Get a first aid kit for the car if you don't have one already.
Get AAA coverage if you don't already have it. You'll be so happy to have it if trouble strikes! Plus, you'll get discounts on some hotels - just ask when you book.
If your road trip is anywhere outside of the US, consider getting travel health insurance.
Arrange for a pet/plant/house sitter or other help such as pet boarding if needed.
Next, get packing! See my packing articles for help. Have fun and remember: it's all about the journey.