Treatment of acute illness in older adults is frequently complicated by the presence of delirium. Delirium is characterized by the development of an altered mental status over the course of hours to days, and can have a fluctuating course. Patients with delirium have difficulty paying attention to their environment, have disorganized thinking, and usually have an altered level of consciousness. While scientists continue to elucidate the pathophysiologic mechanisms associated with delirium, clinicians can identify patients at risk for delirium and diagnose it using valid instruments, such as the Confusion Assessment Method and Confusion Assessment Method for the Intensive Care Unit. Delirium is an independent risk factor for death, institutionalization, and dementia, and resolves in many patients by the time of hospital discharge. For patients admitted to medical units, optimal management of delirium includes reassessment of medications, pain, sleep, nutrition, mobility, need for physical restraints, and bowel and bladder function. The use of antipsychotic medication to sedate delirious patients should be restricted to patients in danger of harming themselves or others and should be used when nonpharmacologic means fail. Multicomponent interventions performed by the hospital care team that address risk factors can prevent delirium in patients in medical units and those undergoing hip fracture repair. This includes attention to the depth of sedation during spinal anesthesia and the addition of regional nerve blocks to patient-controlled analgesia in orthopedic patients, both of which may reduce postoperative delirium. Perioperative use of antipsychotics may further reduce the incidence of delirium, although hospital length of stay has not been routinely reduced. Appropriate management of analgesia, sedation, and delirium in the intensive care unit is also associated with reduced duration of mechanical ventilation, as well as intensive care unit and hospital length of stay. The use of dexmedetomidine, an α-adrenergic receptor agonist, for sedation may reduce intensive care unit length of stay when compared with use of benzodiazepines.