This paper aims to improve understanding of the role of hospitals in the generation of innovations. It presents a systematic and critical review of the interdisciplinary literature that addresses the links between the activities of hospitals and medical innovation. It identifies three major research streams: studies of the contribution of medical research and clinical staff to innovation, analyses of novel practices developed and diffused in hospitals, and evolutionary studies of technical change in the context of human health care. This is a highly heterogeneous body of literature, in which comprehensive theoretical frameworks are rare, and empirical studies have tended to focus on a narrow range of hospitals' innovation activities. The paper introduces and discusses a framework integrating different perspectives that can be used to analyze the functions performed by hospitals at the intersection with different partners in the health innovation system and at different stages of innovation trajectories. On the basis of current gaps in the literature, a research agenda is discussed for a relational and co-evolutionary approach to the study of hospitals as innovators.