Kaiserstraße is largely a pedestrian zone and parking space is quite limited. The best is to use either parking garage Kronenplatz KIT (entry via Fritz-Erler-Str., full day parking fee 5€) or parking garage at Waldhornstraße (german web sites only).
Arrival via Autobahn A5: take exit 44 "Karlsruhe-Durlach", within the exit follow direction "Karlsruhe" (not Durlach!). Drive on the B10 towards Karlsruhe Mitte. Use the second exit in the large roundabout to drive straight ahead and stay on B10. Then turn right into Fritz-Erler-Str. at the next large intersection.
Alternatively, you could also use exit 45 "Karlsruhe Mitte", toward direction "Landau (Pfalz)/Karlsruhe". Take the next exit "Oststadt" and follow the B10 toward Oststadt. Use the second exit in the large roundabout to drive straight ahead and stay on B10. Then turn right into Fritz-Erler-Str.
Arrival in Karlsruhe Main Station: Karlsruhe has an excellent public transportation network. A single ride within city limits is usually included with the long distance train ticket - ask the conductor if in doubt. You can also get around by taxi, however. If you live in the city center, taking the tram/streetcar is highly recommended. The tram stops are located directly in front of the main entrance of the main station. To reach the KIT (Campus South) take the tram 2 to Wolfartsweier, S4 to Bretten/Gölshausen (or Heilbronn), S7/S8 to Tullastr./VBK or (temporarily) S1/S11 to Hochstetten (or Neureut). Get off at the station Kronenplatz. Note that there are actually two different stops named Kronenplatz, located near each other. The Kronenplatz/Fritz-Erler-Str. tram stop is south from Kaiserstraße, so you need to walk northbound first and turn left in Kaiserstraße then. The other Kronenplatz stop ist directly located on Kaiserstraße. Walk westbound on Kaiserstraße (so leave Kronenplatz behind you). The building is located on the right hand side, a few meters after crossing Kronenstr.
Further information at KVV.
Nearest Airports are Frankfurt (FRA) or Stuttgart (STR) both nearly 1 hour by train/car away from Karlsruhe. Frankfurt is as a big hub the larger airport and has a good direct train connection (60min) to Karlsruhe main station.
Further information: Frankfurt Airport, Stuttgart Airport
Arrival at Terminal 2 (Gates D/E): follow the Baggage Claim sign and then look for directions to Terminal 1. You can either use the Sky Line (automated shuttle train, departs every 2-3min) or a Shuttle Bus (departs every 10min). Consider 10-20min total transfer time between terminals. See also Terminal Overview.
Arrival at Terminal 1(Gates A,B,C): follow the Baggage Claim sign (in worst case it may be a 20-25 min walk depending on your arrival gate!).
After leaving the baggage claim area (or transfer to Terminal 1 respectively), follow the directions labeled "Train Stations". It is important that you follow the sign "Long distance trains" ("Fernbahnhof") or Tracks 4-7 (do not follow "Regional trains"). Direct trains to Karlsruhe Main Station are usually departing from Track 5 and are scheduled roughly every 2 hours (departing 11:53, 13:53, 15:53, ...), connections with one transfer via Mannheim are available every other hour. Seat reservation is recommended as the trains may be crowded on the weekend.
Further information available at Deutsche Bahn.