Murine gammaherpesvirus 68 (gammaHV-68) provides a useful model for understanding the initiation of the host response against the gammaherpesviruses. Its value as a model for such studies lies in large part with the inherent difficulties in investigating human responses against EBV and HHV-8 during the first few days following infection. While studies aimed at defining the initiation of gammaHV-68 infection are far from complete, an unexpected trend in this early host response has already emerged. Despite viral replication and the beginnings of viral latency at the site of infection during the first few days following infection, the early host response seems surprisingly inadequate. For example, the pro-inflammatory response is quite limited, and with the exception of the type I interferons, it is not at all clear what innate responses are necessary to provide protection from acute infection. This confusion results from the lack of any significant effect on acute viral replication in several strains of mice which have been made genetically deficient in the expression of particular pro-inflammatory molecules. It is likely that these unexpected results reflect the ability of gammaherpesviruses to carefully control the initial response so that they are efficacious pathogens even in immunocompetent hosts.