In normal and hazardous situations, critical infrastructure systems such as roads, bridges, electricity, gas, and waste treatment facilities play a very crucial role in sustaining communities and industries. It is thus very important to examine the functional and structural stability of these supporting infrastructure systems. An assessment analyzing the criticality of infrastructure systems should be performed before impact of facing extreme events, such as hurricanes, floods, and earthquakes. The criticality assessment involves using a decision support system that incorporates vulnerability and severity assessments to provide emergency agencies and experts, relevant information that will facilitate an enhanced disaster mitigation response. This paper introduces the criticality assessment based on the interrelationships between the critical infrastructure systems, associated industries, and communities. The social, economic, and technical data of the 2008 Midwest floods were collected through interviews, site investigations, and survey questionnaires as a part of this research. Methodology includes the zone of influence of critical infrastructure, activity analysis, social and economic contribution, and priority analysis between the activities and infrastructure systems. Finally, the relative criticality levels of infrastructure systems were derived. DOI: 10.1061/(ASCE)NH.1527-6996.0000084. (C) 2013 American Society of Civil Engineers.