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There is an increasing acknowledgement in the engineering community that the response to this challenge, that is, prevention of catastrophic failure, generally requires a systems approach and necessitates engagement of a large pool of multidisciplinary expertise and the deployment of tools for systems analysis. This multidisciplinary pool includes materials science, structural analysis, manufacturing technologies, quality control and evaluation, mathematics, physics, and probability and reliability. Furthermore, from the scientific point of view, there is also an increasing acknowledgement that addressing the complex engineering problems of today requires the use of concepts and approaches that can account for size and time scaling effects. The Special Issue scope embraces interdisciplinary work aimed at understanding and deploying physics of fatigue and failure techniques, advancing experimental and theoretical failure analysis, modelling of the structural response with respect to both local and global failures, and structural design that accounts for scale and time effects in preventing engineering failures.