HupA, a novel alkaloid isolated from the Chinese medicinal herb Huperzia serrata, is a reversible, potent, and selective inhibitor of AChE. Compared with other well-known AChEIs, such as physostigmine, galanthamine, tacrine, and even donepezil, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. HupA exhibited memory-enhancing efficacy in a broad range of animal models of cognitive impairment. Double-blind and placebo-controlled clinical trials have demonstrated that HupA produced significant improvements in memory deficiencies in aged patients and patients with AD. Furthermore, both animal and clinical safety testings showed that HupA was devoid of unexpected toxicity, particularly the dose-limiting hepatotoxicity induced by tacrine. These encouraging preclinical and clinical findings suggest that HupA is a highly promising candidate for clinical development as a symptomatic treatment for AD and other memory disorders related to a central cholinergic deficiency.