Chapter 2 considers how the diagnosis of frenzy – in its standard definition, an inflammation of the brain or meninges – both shaped and was shaped by anatomical knowledge. Reading the work of the anatomist Thomas Willis (1621–1675) alongside his various sixteenth- and seventeenth-century interlocutors, it situates his anatomical work within a longer tradition of brain–mind cartography. The chapter argues that Willis’s determination to map the functions of the brain onto its structures was driven, in part, by his clinical experiences of frenzy. His explicit hope was that his anatomy would be the foundation stone on which a new, clinically useful ‘Pathologie of the Brain and nervous stock, might be built’. But not all of his hopes for the project were medical in nature, or even this-worldly. Willis also sought to shore up two vital truths, both of which frenzy seemed to undermine: first, that there was a categorical difference between the human soul and that of all other living beings, and second, that the human soul alone would survive the death of the body.