Objective: To review the role of huperzine A in the treatment of Alzheimer's disease (AD). Data Sources: A literature search was conducted through MEDLINE (1950–September week 2, 2008), EMBASE (all years), Google Scholar, International Pharmaceutical Abstracts, and a bibliographic review of relevant articles. Key words included huperzine, huperin, Huperzia serrata, and Alzheimer's disease. Study Selection And Data Extraction: All clinical trials published in the English language that evaluated huperzine A in patients with AD were included in this review. Articles published in Chinese were included when English abstracts or electronic translation technology were available. Data Synthesis: AD is a progressive neurodegenerative brain disorder for which there is no cure; available therapies only decrease cognitive decline. Huperzine A, an alkaloid derived from Chinese club moss (H. serrata), acts as a selective inhibitor of acetylcholinesterase and may also display neuroprotective properties. Preliminary data suggest that huperzine A may improve cognition; studies ranging from 8 to 12 weeks have found improvements in the Mini-Mental State Examination score of 1-5 points. Conclusions: Although use of huperzine A has shown promising results in patients with AD, data supporting its use are limited by weak study design. Largescale, randomized, placebo-controlled trials are necessary to establish the role of huperzine A in the treatment of AD.