Alzheimer's disease is often unrecognized or misdiagnosed in its early stages. Despite the lack of curative treatments, there are compelling reasons why early recognition of Alzheimer's disease may offer substantial benefits. Early evaluation and diagnosis may offer opportunities to enhance patient safety, allow families to plan for the future, provide family education and support, and initiate the best treatment before more substantial neuronal loss occurs. Barriers to early diagnosis include failure of family or physicians to recognize the existence or importance of cognitive/functional changes and/or misperceptions regarding diagnostic requirements and treatment capabilities. There is consensus that high diagnostic accuracy can be achieved clinically, even by nonspecialists, using established criteria and practice parameters. Population-based screening programs for the elderly, genetic testing, yield of routine neuroimaging studies, and the diagnostic value of certain molecular markers remain controversial. This review highlights practical issues related to the initial clinical evaluation and differential diagnosis of Alzheimer's disease.