In this article an epistemological framework is proposed in order to integrate the emergentist thought with systemic studies on biological autonomy, which are focused on the role of organization. Particular attention will be paid to the role of the observer’s activity, especially: (a) the different operations he performs in order to identify the pertinent elements at each descriptive level, and (b) the relationships between the different models he builds from them. According to the approach sustained here, organization will be considered as the result of a specific operation of identification of the relational properties of the functional components of a system, which do not necessarily coincide with the intrinsic properties of its structural constituents. Also, an epistemological notion of emergence—that of “complex emergence”—will be introduced, which can be defined as the insufficiency, even in principle, of a single descriptive modality to provide a complete description of certain classes of systems. This integrative framework will allow us to deal with two issues in biological and emergentist studies: (1) distinguishing the autonomy proper of living systems from some physical processes like those of structural stability and pattern generation, and (2) reconsidering the notion of downward causation not as a direct or indirect influence of the whole on its parts, but instead as an epistemological problem of interaction between descriptive domains in which the concept of organization proposed and the observational operations related to it play a crucial role.