In some respects, one could attribute the eventual decline and fall of the Byzantine Empire to the Sack of Constantinople in 1204, when a large army of Crusaders entered the Byzantine capital and proceeded to kill, rape, destroy, and steal with impunity. In the wake of this appalling atrocity, the Empire was divided up into a number of Crusader-controlled states, thus effectively bringing the Empire to an end, at least temporarily.
Even after this state of affairs came to an end with the restoration of the Byzantine Empire under the Palaiologos dynasty in 1261, Byzantium was never to be quite the same again. The Sack of Constantinople had revealed the fundamental weakness of the Empire, which made it vulnerable to civil unrest and foreign invasion.
A prime example of the intimate relationship between internal disorder and external threats comes in the form of the civil war that raged within the Empire between 1341 and 1347. As a direct consequence of this long and bitter struggle, the Empire became destabilized from within, and the Serbian king Stefan Dušan was able to exploit this internal chaos to his advantage and gain Byzantine territories for himself. The civil war, like the Sack of Constantinople, was one more savage body blow to the Empire from which it would never fully recover.
Over time, as the Byzantine Empire weakened, the neighboring Ottoman Empire was strengthened. Given the importance of Constantinople's strategic position, it was always inevitable that the Ottomans would use their growing military strength and try to seize the Byzantine capital. This they finally managed to do on May 29, 1453, after a siege lasting two months. In capturing Constantinople, the Ottomans brought an end to an empire that had lasted for over a thousand years.