By train: Direct Alvia trains run from Madrid Chamartín to Salamanca in around 2 hours 15 minutes to 2 hours 30 minutes, several times a day. There are also regular services from Valladolid (about 1 hour) and Ávila. Note that Salamanca does not yet have AVE high-speed rail — services use the medium-speed Alvia trains on a conventional line.
By bus: ALSA runs frequent coaches from Madrid (Estación Sur) to Salamanca in around 2.5 hours; also services from Valladolid and other Castilian cities. The bus is often cheaper than the train and drops you at the bus station just west of the old town.
By car: From Madrid, take the A-6 towards Valladolid and then the A-50 west to Salamanca — about 2.5 hours in normal traffic. Parking in the historic centre is limited; there are underground car parks near the Gran Vía.