The present study aims, beyond a succinct presentation of this epistolary body, to provide the elements of historical and theological nature regarding the reporting of the two Saints to the history of the Christian Church, the conflicts existing in the time of these Fathers, and their resolution through direct involvement of St. Isidore. In fact, the questions from which this study starts can be summarized as follows: what are the historical elements (events, situations, conflicts) that grind the Alexandrian Church, led by St. Cyril, and the Pelusio area, where St. Isidore was the spiritual protector? What doctrinal ideas were debated at that time? To which character is Saint Isidore positive? Is the spiritual relationship and the concept of paternity between the two emblematic characters really justified?