I'll add the caveat that I am a Boston driver. Most of the major car companies are in the lot Andrew points out (Hertz, Avis, EuropCar) and there is a shuttle bus that runs between the airport and the rental lot (don't know the frequency). The route that Andrew points out is the one I've taken most and the loop is a multi-lane (something like 4, maybe 5 in some places) road so you do need to be able to manage this. Knowing up front can help since you can stay near the inner lane around until you get near the area where the airport is (and if you haven't been there before look for the gas stations that are just before the airport). The A11 starts right by the airport. My husband and I always rent from the airport rather than in town at a location like Borgo Ognissanti where there are many rental companies since we find it easier to drive the loop above rather than deal with the ZTLs and scooters in Florence (mostly on the return - getting out I find easier). If you don't like rotaries with multiple lanes it may not be for you.