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A fail-safe supply network is designed to mitigate the impact of variations and disruptions on people and corporations. This is achieved by (1) developing a network structure that mitigates the impact of disruptions distorting the network structure and (2) planning a flow through the network to neutralize the impact of variations. Despite the current thinking in the supply network literature, decisions made to manage disruptions are not independent of those made to manage variations associated with operational flow planning. This book proposes a framework of mathematical models and fail-safe supply network designs to manage decisions associated with disruptions and variations concurrently.