Arezzo is on the main Florence–Rome railway line and has frequent direct trains from Florence (about 45 minutes), Siena (about 1.5 hours, with change), and Rome (about 2 hours). The station is at the foot of the old town hill; from there it's a 10–15 minute walk up to the historic centre, or a short taxi ride.
By car, Arezzo sits on the A1 autostrada (Florence–Rome), about 80 km from Florence and 230 km from Rome. The historic centre has limited traffic zones (ZTL) — park at the station or in one of the car parks below the old town and walk up.