Delirium (acute confusion) complicates 15% to 50% of major operations in older adults and is associated with other major postoperative complications, prolonged length of stay, poor functional recovery, institutionalization, dementia, and death. Importantly, delirium may be predictable and preventable through proactive intervention. Yet clinicians fail to recognize and address postoperative delirium in up to 80% of cases. Using the case of Ms R, a 76-year-old woman who developed delirium first after colectomy with complications and again after routine surgery, the diagnosis, prevention, and treatment of delirium in the postoperative setting is reviewed. The risk of postoperative delirium can be quantified by the sum of predisposing and precipitating factors. Successful strategies for prevention and treatment of delirium include proactive multifactorial intervention targeted to reversible risk factors, limiting use of sedating medications (especially benzodiazepines), effective management of postoperative pain, and, perhaps, judicious use of antipsychotics.