Often overlooked in the art historical literature, inscriptions are virtually omnipresent in Ghirlandaio’s oeuvre. They appear as monumental lettering in his Cycle of Famous Men, chapel decorations and altarpieces, as handwritten notes in his St. Jerome and Portrait of Giovanna degli Albizzi, and on a tablet that is pinned to the wall of a painted room in a scene in the Santa Fina Chapel. Some of them address with direct speech those depicted, others appear as historical inscriptions within the narrative, others again simply name figures or give a work’s date of execution. The article draws out how even the most basic inscriptions (often through the choice of their location) are carefully integrated into the semantics of these images. Still, in contrast to contemporaries such as Gozzoli, Filippo and Filippino Lippi, Ghirlandaio apparently showed little interest in the aesthetic or antiquarian dimension of lettering and marked the authorship of his work through the insertion of self-portraits, rather than words or dates. These, it is argued, are regularly employed to forward the cause of the patron. Thus, they appear in painted architectural sites that were associated with the patron. Acting upon his patrons’ taste for ancient words and lettering, Ghirlandaio employed the authority and weight granted to the written word, ancient languages, and classical lettering to heighten the appeal of his paintings among the social elites and to forward their social claims.