The study of hepatitis C virus (HCV) has been hampered by the inability to grow viral clinical isolates in cell culture. Saeed et al. postulated that this was due to the lack of essential factors in cell lines, and transduced human hepatoma cells with a lentivirus-based human complementary DNA (cDNA) library to identify the missing factors. They found a gene product, SEC14L2, which was sufficient to enable replication of HCV replicons and HCV isolates from patient sera in cell culture. HCV replication is known to induce lipid peroxidation, which inhibits viral replication; SEC14L2 seems to counteract this inhibition by enhancing vitamin E-mediated protection against lipid peroxidation, therefore promoting viral replication. The ability to grow HCV isolates from patients in cell culture is expected to further our understanding of HCV biology.