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Adults aged ≥65 years comprise the fastest-growing segment of the United States population, and older adults experience greater morbidity and mortality due to infection than do young adults. Although age is well established as a risk factor for infection, most clinical investigations of infectious diseases in older adults focus on microbiology and on crude end points of clinical success, such as cure rates or death; however, they often fail to assess functional status, which is a critical variable in geriatric care. Functional status can be evaluated either as a risk factor for infectious disease or as an outcome of interest after specific interventions using well-validated instruments. This article outlines the currently available data that suggest an association between infection, immunity, and impaired functional status in elderly individuals, summarizes the instruments commonly used to determine specific aspects of functional status, and provides recommendations for a new paradigm in which clinical trials that involve older adults include assessment of functional status.