Many persons aged 65 years and older encounter new disabilities in activities of daily living after a period of acute hospitalization; this is defined as functional decline. A consequence of functional decline is they are not able to perform essential daily activities, such as bathing, dressing, and walking independently. Recovery from these new disabilities is difficult. Older persons who encounter functional decline report a lower health-related quality of life and are often in need of permanent home care. The systematic in-hospital recording of a patient's functional status prior to hospital stay, early ambulation, and adequate and effective rehabilitation or transitional care can contribute to the prevention of functional decline. However, these interventions are often not applied in clinical practice. Until now, the prevention of functional decline has only been possible in a limited number of older persons. Major research questions include: can all older persons recover from functional decline, which mechanisms contribute most to functional decline and how can these mechanisms be influenced?