Map out the trip ahead of time so you know how long the trip will take, as well as how to get to your destination. Go online (see Resources below) or use an atlas to figure this out.
Make a list of what you'll need on the road and make sure those items are within easy reach once you're in the car. This includes snacks, blankets, pillows, games and anything else that will make the trip more comfortable.
Make everyone wear extra clothing (in layers) when starting out the trip. The extra layers can be taken off as needed, make it easier to adjust to everyone's different temperature needs.
Listen to soothing music while driving to help you stay relaxed. Do not play anything hard or heavy. Suggestions include classical, jazz and oldies.
Play road trip games. Games that can be played in a car can be picked up in almost any bookstore or magazine section. This makes it much more enjoyable for the driver.
Switch drivers if possible. This should be done every couple of hours. The alternate drivers should try to rest or nap during the times they are not driving.
Stop for breakfast, lunch and dinner to keep your energy level up. Do not skip these meals. If you don't want to stop at a restaurant every time, prepare a picnic ahead of time.
Clean the car out during the stops to keep the inside from getting cluttered with trash.
Use your time in the car to converse with the other passengers. This can be precious time to share stories and learn more about each other, away from the distractions of daily life.