Aged humans have almost a 10-fold higher risk of encephalitis due to West Nile Virus than younger humans. In order to study this age-dependent susceptibility, the authors used rhesus macaques as a model for investigating primate immune responses to WNV. The authors infected macaques of different age classes and levels of adaptive cellular immunity with WNV under simulated “natural” conditions. They found that sensitivity of both “adult” and “old” macaques to WNV is actually low, and that they rapidly resolve the circulating viral RNA infection. This suggests evidence of a heightened innate immune system response in macaques, and the authors finally conclude that macaques might not be the best model for vaccine testing against WNV. The authors hope that a different model system will lead to a better understanding of older primates’ greater susceptibility to WNV-based encephalitis. A proper model system is critical, as it will allow us to effectively study the age-based decline of protective immunity, as well as improvements in vaccination strategies and other preventative immune system treatments.