In a search for new hepatitis viruses, two independent groups identified viruses named GB virus C and Hepatitis G Virus, which turned out to be different strains of the same agent Despite its initial ascription to hepatitis viruses, this new virus does not cause any hepatitis. Thus, the term GB virus C is preferred. Soon after its discovery, a significantly better clinical course of HIV infection was demonstrated for patients coinfected with the GB virus C in 1998. These results were confirmed in other further studies, but not in all of them. Importantly, studies not confirming a positive influence usually found a neutral effect. The data for most of the studies had been mainly collected in the time prior to the availability of highly effective antiretroviral therapy (HAART). Since HAART has become available, some authors have reported a beneficial effect while others have shown only a neutral influence of GB virus C on HIV, considering either survival or the degree of response to HAART An explanation for these discrepancies may be that different GB virus C strains exhibit different replication capacities. Understanding the mechanisms by how GB virus C and HIV interact may help find new strategies to fight HIV infection. Some recent in vitro findings have added evidence on how GB virus C might interact with and inhibit HIV replication. In this review, we update the current knowledge on GB virus C, its role in HIV infection in the HAART era, and discuss the potential mechanisms of its beneficial effect.