Historical observations of disorders of language have been reported from Pharaonic medical texts circa 3000 bc, the Hippocratic corpus circa 400 bc, Latin texts circa 1st century ad, through the Renaissance and in various 17th and 18th century texts. In none of the extant historical papers, however, have certain critical elements of aphasia been discussed, i.e. the distinction between a disorder of language and a deficit in its articulatory realization, nor the relation between aphasia and a left hemisphere lesion. This paper discusses the relatively unknown aphasia studies of two 16th and 17th-century physicians, J. Schenck and J. J. Wepfer, with respect to these critical elements. Johannes Schenck (1530–1598) assembled a collection of clinical observations from antiquity to those of his contemporaries; Vol. 1 ( Observationes Medicae de Capite Humano, Basel, 1584) discusses the pathology of the head and face, at least 16 cases of which refer to patients with aphasia. Johannes Jakob Wepfer (1620–1695) wrote a book on the vascularization of the brain and on apoplexy; in addition he wrote (published posthumously) a collection of neurological cases ( Observationes Medico-practicae de Affectibus Capitis Internis & Externis, Schaffhausen, 1727). In the latter he reported on 222 neurological and neurosurgical cases, at least 15 of which had an overt aphasia, almost all due to a left hemisphere lesion. The level of functional and anatomical detail in these case studies invites comparison with the best of the late 19th century classical aphasia literature.