The paper addresses processes of construction and imagination of the enemy in the context of the "horrende guerre d'Italia" affecting the Italian peninsula between the late fifteenth century and the Sack of Rome in 1527. In a historical setting characterised by a widespread perception of instability, traumatic events were interpreted through religious and prophetic categories that provided frameworks for understanding and meaning-making. Within this context, the paper examines the reactivation of long-standing prophetic and scriptural motifs used to interpret the roles of different political actors. Motifs such as the just-chastiser, the second Charlemagne, or, in an antithetical sense, the new Nero were applied flexibly to various protagonists of the conflict, intersecting with pro-French or pro-imperial readings and contributing to the framing of the enemy as a sign of divine judgement. The figure of Charles V represents one of the key reference points within this constellation of meanings. The paper also considers how prophetic models interacted with political motifs and natural and celestial signs in the context of a crisis perceived as extraordinary, giving rise to shifting configurations of the enemy adaptable to different contexts and actors. From this perspective, the conceptualisation of the enemy emerges as a key interpretative device in religious responses to catastrophe.