A central theme that structured Vedāntic–Buddhist dialectics was the definition of ‘substance’. We shall argue that while certain forms of Vedānta and Madhyamaka Buddhism are shaped by the same set of presuppositions regarding ‘substance’, they derive opposed conclusions from this point of departure as they elaborate their conceptual universes. Further, while both Advaita and Viśiṣṭādvaita Vedānta seek to defend against their Buddhist rivals the thesis that the phenomenal world is a ‘dependent substance’, in the sense that it derives its empirical being from the foundational Ground of Brahman, they disagree over this crucial question: ‘precisely how real is this dependent substance?’ Consequently, some of the central disputes between Advaita and Viśiṣṭādvaita can be traced to a basic divergence in their conceptualisations of ‘substance’, which informs their responses to questions such as whether the postulation of a plurality of metaphysically real substances can be logically defended, whether the concept of a ‘dependent substance’ is coherent, whether real relations between the ultimate substance and dependent substances can be explicated without inconsistency, and so on.