On the basis of substantial preclinical data showing the preventive efficacy of ginger and its constituents in vitro and in animal models, as well as a phase I pilot trial indicating that ginger extract is well tolerated in humans, Citronberg and colleagues conducted a pilot trial of ginger extract (2 g/day for 28 days) on biomarkers of cell proliferation [human telomerase reverse transcriptase (hTERT), MIB-1], differentiation (p21waf1/cip1), and apoptosis (Bax, Bcl-2) in colonic mucosa from individuals at high-risk for colorectal cancer. Results from the trial suggest that ginger may reduce proliferation in normal-appearing colorectal epithelium and increase apoptosis relative to proliferation, especially in the differentiation zone of colon crypts. The authors suggest that these results support a larger study to confirm the pilot data. Before proceeding with a larger trial, however, it seems prudent to confirm ginger as a chemopreventive for colorectal cancer in animals, particularly when tested in postinitiation protocols and to identify reliable molecular biomarkers of effect that could be evaluated in clinical trials. Pharmacokinetic studies to examine the distribution and localization of ginger compounds and metabolites in the differentiation and proliferative zones of colonic crypts in animals and humans would also be informative. Finally, because the effects of ginger on normal colonic mucosa seem minimal, consideration should be given to the conduct of future trials in humans with premalignant colorectal disease.