The study of the aetiologies of diseases in Ancient Times is usually a speculative intellectual exercise. When some authors attribute a specific aetiology to an old disease, there is a great risk of committing a methodological error, known as presentism by the modern historiography. The authority of the investigator, more than the weight of the scientific truth, is usually the reason why the diagnosis has remained over the years. The great epidemic of the years 164-165AD and afterwards, could have been smallpox (haemorrhagic form). Claude Galen, the famous doctor, described the symptoms in several books of his great Opera Omnia. For this reason, it is currently known among the scholars as Galen's plague. The epidemic was described for the first time in Seleucia (Mesopotamia). Until now, the actual geographic origin is unknown. We propose here that the beginning might be the kingdom of the old Han dynasty (now the Chinese Popular Republic). The epidemic swept the Roman Empire, from the east to the west, and from the southern to the northern borders. An immediate consequence of the infection was a high morbidity and mortality. In this sense, Galen's epidemic was one of the many factors that caused the fall and destruction of the Roman Empire. On the other hand, there is a general agreement among historians, biographers and researchers that the philosopher emperor Marcus Aurelius Antoninus (121-180AD was affected by the infection in the epidemic wave of 164-165AD. The death of Marcus Aurelius occurred on March 17 in the year 180AD, in Vindobonne, or perhaps Sirminium (near to Vienna). Many authors propose that the cause of the emperor's death was the same epidemic. We consider that it is not possible to demonstrate any of those speculative diagnoses. Finally, the epidemic of 189-190AD, that we have named of Commodus, was probably a different disease to the Galen's plague. There were several kinds of animals affected (anthropozoonoses). In this sense, this infection resembles more the previous Athens plague (430BC) or the epidemic of Justinian (552AD) than that of Galen's.