Add about 1/3 to the normal time it takes to complete a trip. For example, we drove to Boston to visit friends when Isabelle was 5 months old. The trip normally took us a leisurely 8 hours pre-baby; with baby, it was a solid 12 hours. If possible, try to have one parent sitting in the back seat with the kid(s). Try to plan your departure for a time when baby isn’t asleep – that way you get some “play” time, then (hopefully) a nap before you stop for the first time.
Travelling with a breastfed baby is infinitely easier – all she needs is mama. Never be tempted to take baby out of his car seat when driving – much as his cries may be heart-wrenching. Pull off at the next safe spot and have a nurse while dad stretches his legs. If your child is older, bringing along some special snacks that they really enjoy can buy you a little more driving time.
If your trip is longer than 3 hours or so, try planning your route so that there is an attraction somewhere along the way – it will give you something to look forward to that isn’t as far as the final destination. Bringing along an extra pair of hands can be a great help during the drive and at your destination – whether it’s grandma or teenage cousin. Just be sure your “helper” is someone you want to spend your vacation with or it could be no help at all.
My only plug is that we carry a great little toddler travel pillow that’s ideal for road trips.