The paper presents an epistemological perspective on entrepreneurship research, particularly building on the thoughts of Peirce. Drawing from an analogy from the field of medicine we find three general roles, practitioner, scientist, and design scientist. Each role follows a distinct prevalent mode (modus operationis, modus cognitionis, modus transformationis). We characterize the activity of a design scientist, the resultative and processual aspects of the artifact, and present examples in the domain of entrepreneurship. Finally, this paper suggests guidelines that can frame the activities of design scientists in entrepreneurship.