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This paper discusses cross-sector infrastructure interdependencies and key risk considerations, analysis approaches, research and development needs, and the range of interdisciplinary skills required for comprehensive cross-sector analysis. Traditional analysis of interdependencies involves characterization of infrastructure-to-infrastructure linkages to identify the key infrastructure components that, if lost or degraded, could adversely affect the performance of other infrastructures. Such analysis is motivated by the recognition that a series of incidents could interact (cascade) across critical infrastructures to degrade the service upon which all depend. From a risk perspective, cross-sector analysis also must involve identifying and characterizing a wide range of threats (natural and accidental, systems related, and intentional), vulnerabilities (physical and cyber), and consequences of loss (e.g., health and safety, economic, national security, environmental, sociopolitical). Such information provides a foundation for making defensible, cost-effective infrastructure protection and operation decisions to ensure the security and reliability of our interdependent systems.