This chapter explores ethical issues raised by the use of artificial intelligence (AI) in the domain of biomedical research, healthcare provision, and public health. The litany of ethical challenges that AI in medicine raises cannot be addressed sufficiently by current regulatory and ethical frameworks. The chapter then advances the systemic oversight approach as a governance blueprint, which is based on six principles offering guidance as to the desirable features of oversight structures and processes in the domain of data-intense biomedicine: adaptivity, flexibility, inclusiveness, reflexivity, responsiveness, and monitoring (AFIRRM). In the research domain, ethical review committees will have to incorporate reflexive assessment of the scientific and social merits of AI-driven research and, as a consequence, will have to open their ranks to new professional figures such as social scientists. In the domain of patient care, clinical validation is a crucial issue. Hospitals could equip themselves with “clinical AI oversight bodies” charged with the task of advising clinical administrators. Meanwhile, in the public health sphere, the new level of granularity enabled by AI in disease surveillance or health promotion will have to be negotiated at the level of targeted communities.