Possess a valid, current drivers license. Confirm that it is valid well within the date range of the trip and that it has no issues pending against it. Call the local Department of Motor Vehicles or similar state agency that regulates drivers licenses in the U.S.
Take the valid U.S. drivers license on the trip to Mexico, even if entering by plane. The Mexican government recognizes a U.S. drivers license as legal in Mexico, as long as the license is valid in the U.S.
Purchase appropriate car insurance for both a car entering Mexico or a rental car. U.S. auto insurance is not valid in Mexico. At the border and in large towns, there are several agencies available solely for tourists to purchase insurance. For rental cars, consider purchasing the insurance offered by the rental company. Some major credit cards will cover insurance in Mexico, but check individual policies prior to the trip.
Follow driving rules. Most driving regulations are very similar to those in the U.S., with a few standout exceptions. Passengers can drink alcohol while the vehicle is moving, although the driver cannot. In addition, only the driver must wear a seat belt.
Watch for road signs. Road sign graphics differ drastically from U.S. signage, but are somewhat self-explanatory and don't use much Spanish. Go to the website in "Resources" for more information on sign visuals.