BACKGROUND: With the aging of the population, primary care physicians are increasingly expected to manage patients with Alzheimer's disease. For patients with this disease to obtain the best outcomes over the long term, early diagnosis and effective treatment are critical. Currently, cholinesterase inhibitors are the only drugs approved in the United States for the treatment of mild-to-moderate Alzheimer's disease. METHOD: Relevant clinical studies were identified through a search of the MEDLINE database using the terms Alzheimer's disease and donepezil, galantamine, or rivastigmine, using the limits of English language and publication dates of 1995 to 2003. Published studies were selected that provided information on the long-term use, defined as 1 year or longer, of second-generation cholinesterase inhibitors approved by the U.S. Food and Drug Administration for the treatment of mild-to-moderate Alzheimer's disease. RESULTS: 590 references were identified. Of these, 11 studies met the final study criteria, and 10 were selected (1 of the 11 was an interim analysis). CONCLUSIONS: The benefits of sustained long-term treatment with cholinesterase inhibitors have been demonstrated over the last several years. By reducing cognitive and functional decline over time, long-term cholinesterase inhibitor therapy enables patients to stay at home longer and may decrease the burdens faced by patients, caregivers, and society.