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AI applications are poised to transform health care, revolutionizing benefits for individuals, communities, and health-care systems. As the articles in this special issue aptly illustrate, AI innovations in healthcare are maturing from early success in medical imaging and robotic process automation, promising a broad range of new applications. This is evidenced by the rapid deployment of AI to address critical challenges related to the COVID-19 pandemic, including disease diagnosis and monitoring, drug discovery, and vaccine development. At the heart of these innovations is the health data required for deep learning applications. Rapid accumulation of data, along with improved data quality, data sharing, and standardization, enable development of deep learning algorithms in many healthcare applications. One of the great challenges for healthcare AI is effective governance of these data—ensuring thoughtful aggregation and appropriate access to fuel innovation and improve patient outcomes and healthcare system efficiency while protecting the privacy and security of data subjects. Yet the literature on data governance has rarely looked beyond important pragmatic issues related to privacy and security. Less consideration has been given to unexpected or undesirable outcomes of healthcare in AI, such as clinician deskilling, algorithmic bias, the “regulatory vacuum”, and lack of public engagement. Amidst growing calls for ethical governance of algorithms, Reddy et al. developed a governance model for AI in healthcare delivery, focusing on principles of fairness, accountability, and transparency (FAT), and trustworthiness, and calling for wider discussion. Winter and Davidson emphasize the need to identify underlying values of healthcare data and use, noting the many competing interests and goals for use of health data—such as healthcare system efficiency and reform, patient and community health, intellectual property development, and monetization. Beyond the important considerations of privacy and security, governance must consider who will benefit from healthcare AI, and who will not. Whose values drive health AI innovation and use? How can we ensure that innovations are not limited to the wealthiest individuals or nations? As large technology companies begin to partner with health care systems, and as personally generated health data (PGHD) (e.g., fitness trackers, continuous glucose monitors, health information searches on the Internet) proliferate, who has oversight of these complex technical systems, which are essentially a black box? To tackle these complex and important issues, it is important to acknowledge that we have entered a new technical, organizational, and policy environment due to linked data, big data analytics, and AI. Data governance is no longer the responsibility of a single organization. Rather, multiple networked entities play a role and responsibilities may be blurred. This also raises many concerns related to data localization and jurisdiction—who is responsible for data governance? In this emerging environment, data may no longer be effectively governed through traditional policy models or instruments.