Numerous epidemiologic studies showed an inverse correlation between dietary flavonoid consumption and cardiovascular risk, but the exact mechanisms are still largely unknown. Flavonoids exhibit hormetic properties, where low concentrations activate adaptive cellular stress response pathways and thus lead towards cytoprotection, whereas high concentrations are cytotoxic. However, the limited bioavailability of dietary flavonoids doubts the relevance of effective flavonoid intracellular concentrations to induce bioactivity in endothelial cells. Therefore, translocation of flavonoids through the cell plasma membrane must occur via specific transporter proteins. Hereby, we describe the involvement of the membrane transporter bilitranslocase (TC #2.A.65.1.1) as the key underlying molecular mechanism for membrane transport, which might help resolve the enigma of flavonoids bioactivity.