Wetzlar sits on the rail line between Frankfurt and the Ruhr. Direct regional express trains from Frankfurt take about 50 minutes; the InterCity service from Cologne or Düsseldorf via Siegen is roughly 2½ hours from Cologne. The station is a 10-minute walk north of the Altstadt across the Lahn.
By car, Wetzlar is on the A45 ("Sauerlandlinie") between Dortmund and the A3, about 75 km north of Frankfurt. Free parking is available on the Lahninsel directly below the cathedral, which is the most convenient option for a day visit.