Despite the long series of European research projects that has led to the setting of fully reliable seismic design criteria for precast structures, recent earthquakes have shown that a weak point still exists in the proportioning of the connection systems of cladding wall panels. Following this finding, this paper outlines an organic setting of the design problem of precast concrete structures including cladding-structure interaction and describes three possible solutions, namely the isostatic, integrated and dissipative systems. The related fastening arrangements, with the use of existing and innovative connection devices, are also described. This paper comments on the results of the pseudo-dynamic and cyclic tests performed at ELSA Laboratory of the European Joint Research Centre of Ispra (Italy) on a full-scale prototype of precast structure. The conception and the experimental performance of the structure with nine different configurations of either vertical or horizontal wall panel claddings are presented. The analysis of the results highlights the effectiveness of the different solutions in a comparative way