Theoretical and practical issues concerning the multi-faceted task of mitigating the latero-torsional seismic response of a prototypal frame structure with asymmetric mass distribution are approached. Chevron braces with embedded magnetorheological dampers acting on the interstory drift are used to provide energy dissipation. A semi-active control strategy is used to govern the modification of the damper characteristics via feedback. Optimal damper forces are assigned according to a H2/LQG criterion, with respect to which the actual forces are regulated by a clipped-optimal law. A dynamic observer ensures a robust estimation of the state through a non-collocated placement of acceleration sensors. Several theoretical and practical aspects to be addressed throughout the complex process characterizing the full development of a semiactive protection system from the design to the application phase are discussed. Experimental results obtained in the mitigation of the motion induced by ground excitation in a large-scale laboratory prototype, simulating the seismic response of a two-story building, are summarized.