Liver disease as a result of chronic hepatitis C virus (HCV) infection is a global problem. While some HCV infections resolve spontaneously, viral persistence associates with compromised T cell immunity. In this issue of the JCI, Chen et al. and Coss et al. explored virus-specific CD4+ T cell response during HCV infection. Both studies evaluated the HCV-specific T cells of patients with different courses of infection. Chen et al. revealed that initial CD4+ T cell responses are similar during early infection and that T cell failure resulted from loss of the virus-specific T cells themselves. Coss et al. showed that HCV-specific CD4+ T cells temporarily recovered in some women following childbirth. These studies contribute to our understanding of CD4+ T cell functionality during different natural courses of infection, with the notable implication that restoring CD4+ T cell immunity might contribute to controlling HCV infection.