It's not far from the airport, but if you go to the airport first (following the highway signs) it *is* very confusing to find, because the service roads area to the NW of their rental office (between the office and the airport) have had a lot of construction changes that have closed intersections recently. Be aware of this if using a GPS to navigate to or away from the rental office; there is about a 50/50 chance that it will attempt to either send you down a closed road or send you the wrong way down a one-way street.
It is best to approach the office from the south or east, coming westbound on Spruce or northbound across Spruce on O'Brien, even if you are coming from the coast. The closest gas stations are on Cypress, which parallels Spruce a few blocks south.
If you are coming from the coast across the Campbell Causeway, the easiest thing to do is swing south on 60 (aka Memorial Hwy.) and then exit on Cypress and turn left. You can fill up the tank at a station on Cypress and then go a mile or so north on O'Brien until it dead-ends in the Airport Access Road, and then turn left to get to the Nat'l office.
If you're coming from Orlando/WDW, the best choice is to exit highway I-275 on Dale Mabry, turn north and get your gasoline, and then turn left on W. Columbus. The street changes name twice, becoming Boy Scout Blvd and then Spruce. From westbound Spruce, make a right turn on O'Brien, then left on Airport Access Rd.; the return will be less than a mile up on your right (north side of the road.)
(Note that if you look at Google Maps, it says that the National office is ON Spruce. It is not. The office is on the Airport Access Road that runs parallel to Spruce on the north.)
