The aim is to point out the salient stages that led to a momentous change of the whole history of Greek Sic- ily. After a period, started within the VIth century BC, in which the preferred interlocutor of the Siceliots was Carthage, regarded by some Greek cities as a trustworthy international partner and by other cities as a “danger” to fight with and that should have been cancelled, if possible, the Greek-Punic relationship had known for a long time of the Vth century BC a moment of blackout. At the end of this period, lasted nearly seventy years, the North-African city had turned to be interested in Sicily within a deeply changed international context. Even the attitude of Carthage toward the Island was radically transformed. In front of the Dionysios Ist’ politics aiming to create a territorial state, the Punic city as well took care with bigger attention to its own territory, fixing exact borders with the area controlled by Syracuse, up to create, at the end of the IVth century BC, its epikrateia. Meanwhile, the progressive weakening of Syracuse, due to the particularisms and the civic struggles of the Greek poleis, fostered the growth of the Carthaginian power, which more and more often was involved into the inner events of the Sicilian Greekness. Only the action of strong personages such as Timoleon, Agathokles and Pyrrhus, tried to resume the old project of making Greek whole Sicily. Regrettably, prevailed the egoisms and the particularisms, that not only didn’t allow to expel the Carthaginians from Sicily, but also founded the statements of the intervention of another great power, Rome. It was just the Urbs, after a more than 20-years bloody war, culminated in the Egadi Islands battle, that drove out the Carthaginians from Sicily. Unfortunately, the end of the Punic presence in Sicily didn’t clash with the victory of the Greekness, but with a heavy tribute paid through enslaved and sold peoples, destroyed cities, devastated fields and through the loss of the role of Mediterranean power played for many centuries.