The concept of viruses causing neurologic disease in snakes is not foreign to veterinarians due to the importance and prevalence of reptarenaviruses (inclusion body disease) in boas and pythons and ferlaviruses in colubrids and viperids. Unfortunately, a novel viral cause of neurologic disease in a diverse assemblage of snakes, including colubrids, viperids, and pythons, from diverse geographic home ranges, has recently been characterized. Through combined clinical, postmortem, and molecular investigation, picornaviruses distinctly unique from all other families in the Picornavirales have been discovered and associated with neurologic signs, ranging from twitching to flaccid paralysis, and extensive inflammation and neuronal necrosis and dropout of the brain and spinal cord. While much remains to be learned about these viruses, their wide host range and suspected ability of individuals to cross infect snakes of different families make them a concerning pathogen for both captive and free-ranging snakes.