The emperor of Rome, Marco Ulpio Trajano, ruled the Roman Empire from 98 to 117 AD, being the first emperor of non-Italian origin and the man who took the Empire to its maximum geographical extent. Trajan’s death is surrounded by mystery, given Adriano’s controversial adoption as his successor just before his death, as well as rumors of poisoning by his wife, Plotina. In addition, despite the limited literary sources available, episodes of «paralysis», «stroke», «dropsy», diarrhea and nonspecific episodes of «illness» have been documented, related to the worsening of his health the months before his death. His special love of wine and life habits related to the personality of the emperor, could be associated with his delicate state of health during the last year of his government, although it is not possible to rule out other pathological processes with neurological involvement associated with the last years of life of the optimus princeps, which could interfere with his last decisions as ruler. In this article, the historical sources available are reviewed in order to analyze, from the neurological point of view, the last moments of the emperor with which Rome reached its maximum military splendor.