One response to the religious freedoms offered by the Byzantine Empire was the Christian monastic movement. For hundreds of years, many Christians had found spiritual strength through enduring persecution and poverty. Now, with a Christian emperor and the Edict of Milan protecting them, Christians were able to speak and move freely. For some, this “easy” life was unfulfilling and allowed for fleshly distractions. In an attempt to regain the spiritual focus of Christianity's unpopular days, some chose to seclude themselves from society, denying their bodies basic comforts.

This ascetic lifestyle was by no means unique to Christianity. Certain Hindus, Buddhists, Greek brotherhoods, and Jewish groups (such as the Essenes) separated themselves from the world, pursuing a monastic life. The Christian monastic movement originated in Egypt around 300, with Anthony of Alexandria. As the first Christian monk, Anthony taught the earliest known rules for Christian monasticism, which were recorded by Athanasius.

Soon, Christians across the Middle East were choosing the monastic life instead of the world's vices and riches. For example, Basil the Great was a member of a wealthy family from central Asia Minor. After receiving a top-notch education in Athens and Constantinople, Basil visited several well-known monks in Egypt and Syria. The devotion of these hermits inspired Basil to reject the privileged life for a path of poverty, meditation, and learning. Around 360, Basil founded the Basilian monastic order, whose rules remain the model for nearly all of today's Middle Eastern monks.

Finally, Simeon of Antioch took his spiritual quest to the extreme, living atop a sixty-foot pillar for more than thirty years. Known as Stylites (from the Greek word stylos, meaning “pillar”), Simeon and others like him gave up all physical pleasures, enduring cold nights, wet winters, and scorching heat atop their pillars. Viewed as a wise holy man, Simeon's eccentric ways attracted both Christians and polytheists from around the Middle East. Following Simeon's death in 459, many people followed his example, living atop pillars to escape the world's carnality. Eventually, an entire complex was built around his pillar, which became a destination for pilgrims traveling between Jerusalem and Constantinople.