Cars and driving
For the more adventurous or those who want to travel off the beaten track, a rental car is the solution. It is also more economical for large families and more practical if you're carrying lots of luggage. The only road not worth driving is Rome-Florence, which takes 3 times longer than the train. A lot has been written ridiculing the impossible road signs and rude drivers of Italy, about which I have only to say that they're not the worst in the world, and it only takes a bit of patience. At least there is not road rage involving guns here (yet).

Cars can be rented in any city. Major companies tend to have similar rates though shop around on their websites to get the best deal. Some areas are best served by certain companies - for example, for Sicily try Sicily by Car, a subsidiary of AutoEuropa. Other companies are AutoEuropa, Avis and Hertz.

Bus
If you don't want to drive, in some cases you might be stuck taking the bus. There are some towns that are virtually or completely unreachable by train. For example, taking the train to Siena is very impractical. To visit siena you must take a SITA bus from Florence. Most hill towns, both in the north and south of Italy, also must be reached by treacherously driven busses. Each of these is operated regionally; information can be had from your hotel or the local tourist office.