Tacrine, the first drug specifically approved for Alzheimer's disease, produces symptomatic improvement. The theoretical rationale behind treating Alzheimer's disease with tacrine is based on central cholinergic depletion. Tacrine is centrally acting, uncompetitive reversible inhibitor of acetylcholinesterase and butyrylcholinesterase. Multiple clinical trials support the effectiveness of tacrine in Alzheimer's disease. High dosages of tacrine are required for efficacy, with the potential for hepatic and mild gastrointestinal adverse effects. However, the benefits of tacrine currently outweigh its risks, and a trial of the drug should be offered to patients. As clinical experience with tacrine increases, the long term risk-benefit equation may be refined.