The diagnosis of Alzheimer's disease (AD) is done by a careful history, requiring reliable informants and serial observations. The main differential diagnosis is depression, delirium, and inappropriate use of psychotropic drugs. Other common causes of dementia such as vascular, Lewy body disease, frontal lobe degeneration, can be distinguished by the pattern of symptoms and findings on the physical examination. A minimal amount of laboratory investigation is usually required. The natural history of AD, with progressive involvement of cognition, activities of daily living and behaviour, justifies the need of outcome variables addressing these specific symptomatic domains. These are complemented by global clinical assessment tools for disease staging and disease progression. A new challenge is to select from outcome variables used in clinical investigations the most appropriate tools for regular clinical practice.