Postoperative delirium represents a serious complication after major surgery. Patients suffer from anxiety, hallucinations and delusions, and have higher postoperative morbidity and mortality. Generally, the role of acetylcholine deficiency in delirium pathophysiology is widely accepted. How this pathologic state evolves in the postoperative period is the topic of this paper. Systemic inflammation as a response to surgical trauma causes diffuse microcirculatory impairment. The most relevant pathologies include leukocyte adhesion to vessel lining, endothelial cell swelling, perivascular oedema, narrowing of capillar diameters, and lowered functional capillary density. These morphological changes lead to a decrease of nutritive perfusion and to longer diffusion distance for oxygen. Because acetylcholine synthesis is especially sensitive to low oxygen tension, symptoms of its deficiency readily develop. Therapeutic tools to modulate excessive inflammation are available, therefore new strategies of delirium treatment should be implemented in clinical praxis, as well as in preventive measures.