While it is widely recognised that, on the one hand, reductionistic approaches are inadequate to deal with the multifactorial and complex nature of health and disease, and on the other hand, a system level understanding of the normal and pathological functioning of biological systems is sorely needed; no clear procedure have been put forth about the actual implementation of such a program. In this paper we review the tools and the mode of thinking that systems biology has set forward in the last twenty years, pinpointing its key methodological and epistemic aspects, together with the technical obstacles and conceptual limitations that it is faced with. A new approach conducive to a system level understanding of biomedical systems is thus, proposed.