The "Doctrine of signatures" occupies an important position in the scientific and medical thinking from the 16th century onwards. In a universe conceived as a vast system of correspondences, in particular between our world and God's will, the signatures are the visible marks of the purpose of divine creation. In therapeutic practices they indicate the virtues of plants by their resemblance to specific organs they are supposed to be able to cure. This Doctrine, like the medical practices it served, is often relegated to a pre-modern knowledge. Shifting the perspective from its doctrinal content to its practical applications in medical treatises, this article suggests that the graphical and scriptural treatment of signatures by Oswald Crollius (ca 1560-1609), Giovanni Battista Della Porta (1534-1615) and Wolfgang Ambrosius Fabricius (1653) allowed the invention of an instrument which, by formalising and systematising the correspondences between plants and organs, made possible a practical use in which metaphysical and religious justifications were not explicitly involved any more, precisely these justifications which resulted in confining this doctrine outside of modernity.