The Rüsselsheim train disaster occurred near the station on 2 February 1990, killing 17 persons and severely injuring 145.

Rüsselsheim lies in the area served by the Rhein-Main-Verkehrsverbund (Rhine-Main Transport Association, RMV).

It is used by Rhine-Main S-Bahn trains operated by DB Regio and buses.

Rüsselsheim station is also served by Regional-Express trains running between Koblenz Hauptbahnhof and Frankfurt (the Mittelrhein-Main-Express, RE 2) and between Saarbrücken Hauptbahnhof and Frankfurt (Rhein-Nahe-Express, RE 3), each running every two hours, resulting in an approximately hourly service as far as Mainz.

Rüsselsheim Bahnhof Südseite bus stop to the south of the station is served by routes L1, 22, 24, 28, 72, and 752.