The Patient-Centered Outcomes Research Institute (PCORI) is a nonprofit, nongovernmental organization established by the U.S. Congress to fund comparative clinical effectiveness research focusing on patient-centered outcomes through the engagement of stakeholders. Evaluation of emerging healthcare innovations is one of PCORI’s five National Priorities for Health. One such initiative is PCORI’s Emerging Technologies and Therapeutics Reports program, established to provide timely overviews of evidence on new drugs and other healthcare technologies. This article provides an overview of completed and ongoing Emerging Technologies and Therapeutics Reports including lessons learned to date. In addition to systematic searches, systematic selection of studies, and transparent reporting of the available evidence, informed by a select number of stakeholders (i.e., key informants), these reports focus on contextual factors shaping the diffusion of emerging technologies that are often not reported in the medical literature. This article also compares processes and methodologies of health technology assessments (HTAs) from a selected number of national and international publicly funded agencies with a goal toward potential future enhancement of PCORI’s Emerging Technologies and Therapeutics Reports program. HTAs vary considerably in terms of funding, types of assessments, the role of manufacturers, stakeholder engagement, timeline to complete from the start to the finish of a draft report publication, and communication of uncertainty for informed decision making. Future Emerging Technologies and Therapeutics Reports may focus on rapid reports to support a more expedient development of evidence. Future research could explore the role of contextual factors identified in these reports on targeted evidence generation.