Pigs experience biological stress such as physiological, environmental, and social challenges when weaned from the sow. The process of weaning is one of the most stressful events in the pig's life that can contribute to intestinal and immune system dysfunctions that result in reduced pig health, growth, and feed intake, particularly during the first week after weaning. Technological improvements in housing, nutrition, health, and management have been used to minimize some of the adverse effects of weaning stress, but a greater understanding of the biological impact of stress is needed to improve strategies to overcome weaning stress. The focus of this review paper is to briefly describe how the biological stress associated with weaning impacts intestinal morphology, structure, physiology, and intestinal immune responses that can impact subsequent production efficiencies such as growth, intake, morbidity, and mortality.