From the start, the régime faced numerous problems. The Turks of Asia Minor had since 1263 been raiding and expanding into Byzantine territory in Asia Minor. Anatolia, which had formed the very heart of the shrinking empire, was systematically lost to numerous Turkic ghazis, whose raids evolved into conquering expeditions inspired by Islamic zeal. With a decreasing source of food and manpower, the Palaiologoi were forced to fight on several fronts, most of them being Christian states: the Second Bulgarian Empire, the Serbian Empire, the remnants of the Latin Empire and even the Knights Hospitaller.
The loss of land in the east to the Turks and in the west to the Bulgarians was complemented by two disastrous civil wars, the Black Death and the 1354 earthquake at Gallipoli, whose destruction and evacuation allowed the Turks to occupy it. By 1380, the Byzantine Empire consisted of the capital Constantinople and a few other isolated exclaves, which only nominally recognized the Emperor as their lord. Nonetheless, Byzantine diplomacy coupled with the adroit exploitation of internal divisions and external threats among their enemies, and above all the invasion of Anatolia by Timur, allowed Byzantium to survive until 1453. The last remnants of the Byzantine Empire, the Despotate of the Morea and the Empire of Trebizond, fell shortly afterwards.
However, the Palaiologan period witnessed a renewed flourishing in art and the letters, in what has been called the "Palaiologian Renaissance". The migration of Byzantine scholars to the West also helped to spark the Renaissance in Italy.
Following the Fourth Crusade, the Byzantine Empire had fractured into the Greek successor-states of Nicaea, Epirus and Trebizond, with a multitude of Frankish and Latin possessions occupying the remainder, nominally subject to the Latin Emperors at Constantinople. In addition, the disintegration of the Byzantine Empire allowed the Bulgarians, the Serbs and the various Turcoman emirates of Anatolia to make gains. Although Epirus was initially the strongest of the three Greek states, the Nicaeans were the ones who succeeded in taking back the city of Constantinople from the Latin Empire.
The Nicaean Empire was successful in holding its own against its Latin and Seljuk opponents. At the Battle of Meander Valley, a Turkic force was repelled and an earlier assault on Nicaea led to the death of the Seljuk Sultan. In the west, the Latins were unable to expand into Anatolia; consolidating Thrace against Bulgaria was a challenge that kept the Latins occupied for the duration of the Latin Empire.