Based on a study of a network of 170 fab labs and makerspaces, this article investigates the role that such ‘fabrication spaces’ can play in fostering 21st century skills. Using a combination of the two main 21st century skills frameworks—DigComp and EntreComp—developed by the EU Commission, we study by the means of two combined qualitative research methods– semi-structured interviews of 13 fab lab/makerspace founders, followed by a focus group with founders and policymaker—the entrepreneurial and digital skills that are fostered by these fab labs and makerspaces. Our results are that while fab labs and makerspaces naturally foster some entrepreneurial 21st century skills, covering the whole range of those skills necessitates to proactively develop specific activities, which might require specific support policies, as fab labs and makerspaces may not have, themselves the required skills. In regard to technical skills, fab labs and makerspaces enable to develop skills beyond what is generally considered as 21st century digital skills, because they combine digital skills with hands-on ‘making’ skills, since they are themselves mixed environment, both digital and physical. Consequently, the growing importance of ‘maker technologies’ may force to redefine what 21st century skills should be.