Resveratrol has been proposed to prevent tumor growth and the di_erent steps of carcinogenesis; nevertheless, these biological e_ects are sometimes discordant between di_erent cell types. Several hypotheses and works have suggested that the metabolism of resveratrol could be at the origin of a di_erent cellular response. We show here, using colorectal tumor cell lines, that the biological e_ects of RSV result mainly from its carriage by carriers of the superfamily of ABC transporter, i.e., P-gP, MRP, or BCRP. Using cell lines overexpressing these di_erent transporters, we have been able to highlight the importance of P-gP in the response of cells to RSV. These results were confirmed by invalidating the gene coding for P-gP, which restored the sensitivity of colorectal cells resistant to the polyphenol. Subsequently, the status of P-glycoprotein expression is an important element to be taken into consideration in the cytotoxic activity of resveratrol in colorectal cancer cells.