G. W. Leibniz (1646–1716) did not contribute directly to scientific discoveries in the life sciences, but he provided several relevant analyses on methods of investigation applicable to complex, and in particular organic, phenomena. Leibniz's theory of organic bodies and his methodological model had deep and broad implications for the development of physiology at the turn of the seventeenth and eighteenth centuries. This paper focuses on a methodological issue which divided natural philosophers and physiologists during the early Enlightenment—about which Leibniz supported original viewpoints which have kept a certain relevance, mutatis mutandis, in later contexts. The issue in question concerns the relation between the surface organization of phenomena and the deeper organization of underlying micro-structures and micro-processes. In a search for the sufficient reason for phenomena, hypothetical models are called upon to provide determining reasons for surface effects. These reasons represent processes involving micro-mechanisms combined so as to account for the emerging organization.