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This paper examines the potential for breeding stress resistance in pigs through an understanding of the physiology of the stress response and its associated genetic basis. Pigs reared in commercial units can encounter numerous concurrent stressors that can have a negative impact on performance and welfare. Stress induces physiological and behavioural responses that are multidimensional, consisting of a complex neuroendocrine and immune signalling milieu. Some stress-related genetic parameters have been identified using conventional genetic approaches applied in experimental models. However, these traits do not capture the complexity of the stress response. As a result, the molecular mechanisms underlying the variation associated with stress resistance in pigs in a commercial environment is poorly understood. Gene expression profiling is a powerful tool that can be applied to systematically elucidate stress response pathways and networks. Consequently, gene expression technologies have been applied to identify some putative stress-regulated genes. Further application of these and more traditional technologies will aid in elucidating stress resistance using gene expression as a measure of phenotypic variation at a molecular level. It is envisaged that in the future, tools for selecting for stress resistance could eventually be applied on-farm to enhance production, health and welfare status.