Cultural heritage artifacts and buildings are under a constant thread of destruction during devastating earthquakes. Any intervention should be such that it neither violates their form nor changes drastically their structural behavior and should be reversible. In addition, the materials to be used must be compatible with the ones the monument is constructed of. Traditional seismic retrofitting techniques have the disadvantage that most of them violate the above conditions. An alternative approach is the use of innovative seismic-protection systems to enhance the seismic resilience of cultural heritage against the effects of earthquakes, which is reported in this chapter. The potential of seismic-isolation strategy to mitigate the seismic risk of museum artifacts will be first exploited. Subsequently, the state of the art of the use of energy-dissipation devices, such as viscous dampers and shape memory alloys, as well as innovative materials such as FRPs, for the protection of monuments and historic structures will be presented.