The Islamic Empire started its tumultuous and rapid expansion from the year 622 A.D. (the year of Mohammed's Egira). This rapid growth coincided with the epidemic spread of the bubonic plague in the Middle East. Although a first epidemic event had been documented in the year 570 A.D. (pre-Islamic phase), in the Arabic peninsula, classically according to M.W. Dols five severe episodes of plague sub-epidemics are considered in the middle-eastern geographic area: the first occurred in 627 and 628 A.D., the fifth in 716 A.D.. Anyway, we may state that at the onset of Islam the geographic region including Egypt, Palestine, Syria, Iraq, and Iran was involved by endemic plague. In their work, on the ground of a literature review, the Authors describe the characteristics of the epidemic phenomenon, and analyze the how the plague affected the interpretation of Prophet's Koran and Hadits. The passive attitude demonstrated by many Muslims during early Islam was not shared by all believers, since others moved towards a more soft approach, which included the behaviour of the so called moving aside , when the contagion was of concern. The epidemic plague significantly contributed to the weakening of the Eastern Roman Empire, and the rapid decline of the Persian Empire, while during the early expansion phases of Islam, it indirectly favoured the nomadic Arab tribes which, moving on desert or semi-desert territories, succeeded in escaping the contagion more easily. Subsequently, when the Arab population became sedentary, after occupying the conquered cities, this initial advantage was significantly reduced.