In order to deal with the complexity of biological systems and attempts to generate applicable results, current biomedical sciences are adopting concepts and methods from the engineering sciences. Philosophers of science have interpreted this as the emergence of an engineering paradigm, in particular in systems biology and synthetic biology. This article aims at the articulation of the supposed engineering paradigm by contrast with the physics paradigm that supported the rise of biochemistry and molecular biology. This articulation starts from Kuhn's notion of a disciplinary matrix, which indicates what constitutes a paradigm. It is argued that the core of the physics paradigm is its metaphysical and ontological presuppositions, whereas the core of the engineering paradigm is the epistemic aim of producing useful knowledge for solving problems external to the scientific practice. Therefore, the two paradigms involve distinct notions of knowledge. Whereas the physics paradigm entails a representational notion of knowledge, the engineering paradigm involves the notion of ‘knowledge as epistemic tool’.