Epidemiological data and in vitro studies on cancer chemoprevention by tea polyphenols have gained attention recently from the scientific community, nutritionists, the pharmaceutical industry, and the public. Despite the several efforts made recently to elucidate the molecular basis for the anticancer activity of these natural products, little correlation has been found thus far between the putative protein targets of compounds found in tea extracts and levels found in plasma after tea consumption. Here, by using a combination of nuclear magnetic resonance binding assays, fluorescence polarization assay, and computational docking studies, we found that certain green tea catechins and black tea theaflavins are very potent inhibitors (K(i) in the nanomolar range) of the antiapoptotic Bcl-2-family proteins, Bcl-x(L) and Bcl-2. These data suggest a strong link between the anticancer activities of these tea polyphenols and their inhibition of a crucial antiapoptotic pathway, which is implicated in the development of many human malignancies.