The soil-foundation-structure interaction affects significantly the seismic response of bridges by changing both their stiffness and damping characteristics, especially for soft soils, so that the results obtained from ordinary fixed-base analyses may become unrealistic. In such cases soil-structure interaction has to be considered in the analyses. The paper focuses on the effects of soil-structure interaction in multi-span viaducts on pile foundation. In the first section, a procedure to include the effects of soil-structure interaction in the nonlinear response of bridges is presented. This is based on the domain decomposition technique: kinematic interaction analysis is performed in the frequency domain by means of a procedure accounting for radiation damping, soil-pile and pile-to-pile interaction; the non-linear inertial interaction analysis is performed in the time domain by using a finite element model of the superstructure. Suitable lumped parameter models are implemented to reproduce the frequency-dependent compliance of the soil-foundation systems.In the second section, some results of nonlinear dynamic analyses performed on a set of nine bridges designed on soft homogeneous soils by means of a direct displacement approach are presented. The seismic response of bridges, subjected to a set of real accelerograms, is compared with those given by fixed base models demonstrating at what extent and in which cases, soil-structure interaction is important and how it modifies the ductility demands of piers.