This dissertation presents a methodology for the refined, reliable, integrated and versatile assessment of the impact of earthquakes on civil infrastructure systems by using free-field and structural instrumentation as well as hybrid simulation. The methodology is presented through a seamlessly-integrated, transparent, transferable and extensible software platform, referred to as NEES Integrated Seismic Risk Assessment Framework (NISRAF). The software tool combines all necessary components in order to obtain the most reliable earthquake impact assessment results possible. The components are (i) hybrid simulation, (ii) free-field and (iii) structural sensor measurements, (iv) hazard characterization, (v) system identification-based model updating, (vi) hybrid fragility analysis and (vii) impact assessment software.NISRAF has been built and demonstrated via applications to an actual test bed in the Los Angeles area. Based on an instrumented six-story steel moment resisting frame building and free-field station records, site response analysis was performed, and hazard characterization and surface ground motion records were generated for further use during the hybrid simulations and fragility analyses. Meanwhile, the finite element model was built, and the natural frequencies and mode shapes were identified using suitable algorithms. The numerical model was updated through a sensitivity-based model updating technique. Next, hybrid simulations—with the most critical component of the structural system tested in the laboratory and the remainders of the structure simulated analytically—were conducted within UI-SIMCOR and ZEUS-NL, both software platforms of the University of Illinois. The simulated results closely matched their measured counterparts. Fragility curves were derived using hybrid simulation results along with dispersions from research on similar structures from the literature. Impact assessment results using the generated hazard map and fragility curves correlated very well with field observations following the Northridge earthquake of 17 January 1994.The novelty of the developed framework is primarily the improvement of every component of earthquake impact assessment and the integration of these components—most of which have not been deployed in such an application before—into a single versatile and extensible platform. To achieve seamless integration and to arrive at an operational and verified system, several components were used innovatively, tailored to perform the role required by NISRAF. The integrated feature brings the most advanced tools of earthquake hazard and structural reliability analyses into the context of societal requirement for accurate evaluation of the impact of earthquakes on the built environment.