Chi-rho ⳩ is universally known as the Christian monogram, consisting of the first two letters of the name Χριϲτόϲ. In ancient times, it coexisted with other common signs, the staurogram ⳨ and stauros ϯ, both connected to the Holy Cross of Jesus. An analysis of the development of these signs in papyrological evidence from Hellenistic, Roman, and Late-Antique Egypt allows us to track the everyday use of these writing strategies from their pre-Christian origins onward. While the staurogram and stauros are extensively employed in late documents to place texts under God’s protection, the chi-rho developed in a distinctive way. It originated in Ptolemaic cursive handwritings as a simple monogram, inconsistently abbreviating words beginning with χρ-, and survived with a similar function in Roman and Byzantine documents, though mostly in other χρ-words and terms characteristically containing those letters (e.g. χειρόγραφον, χαίρειν). A specific field examined is that of medicine, where it indicated the imperative χρῷ “use” in prescriptive texts, and eventually became a graphic symbol in medical recipes and lost its linguistic role. In only one document is the monogram employed to indicate Christ’s name. Possibly, the extensive use of ⳩ in documentary writings prevented the Christian meaning of the monogram from being employed in non-literary papyri. This chapter discusses these complex interactions, attempting to outline the interplay between writing strategies, symbolic thought, and the materiality of written texts from a semiographic point of view.