Recent flurries of literature on the beneficial effects of GB virus type C (GBV-C), a hepatitis C-related virus, in HIV-1 coinfected individuals have raised the possibility of its potential use as a preventive vaccine in people with a high risk for HIV-1. However, these findings are still controversial, and the mechanisms contributing to the apparent beneficial effects of GBV-C are still unresolved. Researchers debate whether the beneficial effects of coinfection of GBV-C in HIV-1-infected individuals are due to GBV-C viremia or rather the presence of GBV-C anti-E2 antibodies. We review the strengths and weaknesses of various aspects of the GBV-C debate and propose a new perspective involving intracellular molecular events that attempts to synthesize numerous contrasting perspectives and ideas, while suggesting new directions for future research in this area.