The attention devoted to Industry 4.0 by scholars, managers and policy makers has grown exponentially in the last few years. The goal of this paper is to empirically investigate the main barriers and difficulties faced by small and medium sized enterprises in Industry 4.0 implementation. We perform a systematic literature review on the topic and conduct some focus group studies in four countries (USA, Italy, Austria, and Thailand). We identify a set of barriers and obstacles and classified them into six categories: economic-financial, cultural, competencies/resources, technical, legal, and implementation process. The results of the study have significant implications for both scientific research and management practice.