During the Middle Ages (400–1500 CE), the Christian clergy strongly influenced what is known as manuscript culture, a period in which books were painstakingly lettered, decorated, and bound by hand. This period also marks the entrepreneurial stage in the evolution of books. During this time, priests and monks advanced the art of bookmaking; in many ways, they may be considered the earliest professional editors. Known as scribes, they transcribed most of the existing philosophical tracts and religious texts of the period, especially versions of the Bible. Through tedious and painstaking work, scribes became the chief caretakers of recorded history and culture, promoting ideas they favored and censoring ideas that were out of line with contemporary Christian thought.

Many books from the Middle Ages were illuminated manuscripts. These books featured decorative, colorful designs and illustrations on each page, often made for churches or wealthy clients. Their covers were made from leather, and some were embedded with precious gems or trimmed with gold and silver. During this period, scribes developed rules of punctuation, making distinctions between small and capital letters, and placing space between words to make reading easier. (Older Roman writing used all capital letters, and the words ran together on a page, making reading a torturous experience.) Hundreds of illuminated manuscripts still survive today in the rare book collections of museums and libraries.