The Hippocratic Aphorisms had a profound influence on subsequent generations; they not only shaped medical theory and practice, but also affected popular culture. Galen (d.c.216) produced an extensive commentary on this text, as did other medical authors writing in Greek, Latin, Arabic, and Hebrew. The Arabic tradition is particularly rich, with more than a dozen commentaries extant in over a hundred manuscripts. These Arabic commentaries constituted important venues for innovation and change, and did not merely draw attention to scholastic debates. Moreover, they had a considerable impact on medical practice, as the Aphorisms were so popular that both doctor and patient knew them by heart. The present paper will highlight a number of examples that illustrate how this rich commentary tradition can be interpreted and analysed in an interdisciplinary way. It will address the question how the medical exegetical tradition, as exemplified by the Arabic commentaries on the Aphorisms, functioned and developed over time. It will produce evidence for innovation and change in what is sometimes regarded as a scholastic genre. These innovations occur on the level of theory, practice and social interaction.