Abstract Pseudorabies virus (PRV) is an alphaherpesvirus that causes a disease of economic impact in swine. Studies on the molecular biology and pathogenesis of PRV are well advanced. PRV has a striking neurotropism and can establish latent infections in the peripheral and central nervous system. Many parallels exist between PRV pathogenesis in animals and the neurotropic human herpesviruses. Since work can be done with the natural host, model systems can be evaluated directly—something difficult, if not impossible, to do with the human viruses. This review focuses on the ability of PRV to infect the mammalian nervous system, with a specific emphasis on transneuronal spread, the host response to neuronal infection and latency.