Julie Bryant and David Liebovitz, MD, Northwestern Memorial Hospital, and Adam Theall from Impact Advisors, review the evolution of clinical data exchange strategies and solutions, with a focus on contemporary and emerging technologies. The discussion covers the key drivers of clinical data exchange within and beyond a single enterprise, including available solution architectures and data models, current limitations, technical prerequisites and enablers, and cost/benefit considerations. They describe these factors in the context of NMH’s strategic approach to the selection of a vendor for next-generation interoperability. They also highlight the technology environment at NMH, outline the business and technical considerations of the selection process, and describe NMH’s short and long term goals for their interoperability initiative.