The functionality maintenance of European infrastructures like bridges is acquiring more and more importance due to the huge economic losses related to the interruption of their regular service. In particular, fatigue represents one of the most common failure modes occurring in steel and steel–concrete composite bridges: most failures in steel structures are related to fracture and fatigue. Railway bridges endure millions of stress cycles during their life and they are expected to be highly vulnerable to such phenomena. Phenomena like ‘vibration induced’ and ‘distortion induced’ fatigue are still partially uncovered by actual design codes and they represent critical aspects for the assessment of existing bridge remaining life and for the design of new bridges. The European research project FADLESS ‘Fatigue damage control and assessment for railways bridges’, funded by the Research Fund for Coal and Steel, aims at defining innovative technical guidelines for the assessment and control of existing and new bridges with regard to fatigue phenomena induced by vibrations and distortions produced by train passages. The project combines experimental and numerical techniques to study fatigue cracking induced by vibration and distortion phenomena taking into account the dynamic train–bridge interaction effects and the actual traffic spectra on European railway lines. In the present paper, preliminary analyses performed on the Italian case study, the Panaro Bridge, are being reported upon. Results obtained by standard fatigue assessment according to Eurocode rules were compared with the actual fatigue cracks found in the deck secondary components. A preliminary critical review of adopted fatigue assessment methodologies was carried out. Moreover, experimental tests were designed and performed on the bridge in order to identify global and local vibration modes and to evaluate the strain time-histories under train passages of critical details. Finally, experimental global/local mode shapes were compared to numerical results from the preliminary FE bridge model.