Civil engineers, in particular, have the primary responsibility for the design and planning of civil structures, including protective systems to minimize losses of lives and economies during extreme hazard events. Structural failures in recent earthquakes and hurricanes have exposed the weakness of current design procedures and shown the need for new concepts and methodologies for building performance evaluation and design. Although the uncertainty of seismic load has been well recognized by the profession, the incorporation of uncertainty in most building code procedures have been limited to the selection of design loads based on return period. To strike a balance between the possible high initial cost and potential large losses over the structure's lifetime, the life-cycle cost and the uncertainty in the hazards and system capacity need to be carefully considered. Moreover, to strictly enforce performance goals, the target probabilities need to be set directly for the limit states rather than for the design earthquake or hurricane etc. Therefore, the total cost over the life time of the structure should be considered when optimizing the design for natural hazard. The future or damage cost of the structure due to natural hazard is calculated based on quantitative risk assessment (QRA). This paper presents a methodology for the design optimization based on the QRA. A case study for a three story residential wood building is presented in order to demonstrate the concept.