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Industry 4.0 is spilling out from manufacturing to healthcare. In this article, we provide a brief history and key enabling technologies of Industry 4.0, and its revolution in healthcare-Healthcare 4.0-and its reshaping of the landscape of the entire healthcare value chain. We discuss the shift in the system design paradigm from open, small, and single loop to closed, large, and multiple loops. We provide the example of a Caregiving Home, and discuss emerging research topics and challenges, including healthcare big data, automated medical production, healthcare robotics, and human-robot symbiosis. Relevant papers published in this special section are also presented.