This paper contains the results of a study on soil-structure interaction (SSI) problems for reinforced concrete structures under seismic excitation. Preliminary results are applied to the case study of an Italian bridge situated at a critical mountain crossing passage featuring complex topography. This study has mainly two objectives. The first objective consists of studying the effects of seismic waves amplification in the superficial soil layers, which can easily induce structural members to undergo critical stress states during an earthquake. The second objective is to investigate critical issues related to the computational modeling of SSI problems, in order to set up a reliable procedure for modeling the soil-foundation-structure system. In order to simulate seismic wave propagation in specific geotechnical conditions and its effects on the structures, the soil was explicitly included in the analyses, rather than using site-specific multiplicative coefficients for the acceleration. A significant portion of the infinite soil domain below the structure was modeled and the ground motions were applied as stress histories at the base of the model. Some crucial issues involved in the numerical approach to SSI problems were taken into account, such as soil domain reduction, spurious seismic waves radiation damping and meshsize influence on the wave frequency filtering. Results obtained from the numerical investigation indicate that the bridge behavior can be noticeably influenced by superficial soil layers. The study confirms the importance of considering the interaction between the soil and the superstructures when performing pseudo-static and dynamic analyses of reinforced concrete structures.