This region is best explored by car, and if you plan to go beyond the main sights, your own wheels are essential. Driving to Kalambaka or Ioannina from Athens takes the greater part of a day. To reach Ioannina take National Road west past Corinth in the Peloponnese, crossing the magnificent Rion–Antirion bridge. The total trip is 445 km (276 miles). For Kalambaka, take National Road north past Thebes; north of Lamia there's a turnoff for Trikala and Kalambaka (a total of 330 km [205 miles]). The drive from Thessaloniki takes around 5 hours and winds you over the mountains and river valleys of Kozani and Grevena on National Road.
The road from Ioannina to Metsovo to Kalambaka is one of the most scenic in northern Greece, but it traverses the famous Katara pass, which is curvy and can be hazardous, especially December through March (snow chains are necessary). If you are traveling with a few people, it might be more relaxing and almost as economical to hire a taxi to drive you around, at least for a day.
You can rent a car from either Avis, Budget, or Hertz at the Ioannina Airport. Avis also has an office in town.
Avis Car Hire. Dodonis 71, Ioannina, Epirus, 453 32. 26510/46333; www.avis.gr/greece/car-rental/Ioannina_car_hire.htm.