Montepulciano is a few miles from the A1 Autostrada as well as the more scenic SS2 from Rome to Florence. Cars are not allowed inside the historical old town except with a permit, available from hotels so park in one of the numerous lots at the edge of the town. Be warned that the lots fill up quickly in late summer, the height of the tourist season.
Buses, departing from Piazza Pietro Nenni, connect Montepulciano with many other Tuscan cities: Siena 75 minutes, 4/day none on Sunday, Pienza 30 minutes, 8/day, Montalcino 1 hour 10/day, change in Torrenien and Chiusi hourly. Route #146 into Montepulciano is quite scenic. See Tuscany#Get_around for tips.
If you are walking into town from the bus station autostazione in Italian, there is a pedestrian short-cut with both an elevator and stairs to the top of the cliff. The entrance is through a portal on Via delle Lettere at the corner of Piazzale dello Sterro, about 50 m from the bus station.