The design of an interregional high-voltage transmission system in the US is a revolutionary technological concept that will likely play a significant role in the planning and operation of future electric power systems. Historically, the primary justification for building interregional high-voltage transmission lines in the US and around the world has been based on economic and reliability criteria. Today, the implementation renewable portfolio standards, carbon emission regulations, the improvements in the performance of power electronic systems, and unused benefits associated with capacity exchange during times of non-coincident peak demand, are driving the idea of designing an interregional high-voltage transmission system in the US. However, there exist challenges related to technical, economic, public policy, and environmental factors that hinder the implementation of such a complex infrastructure. The natural skepticism from many sectors of the society, in regards to how will the system be operated, how much will it cost, and the environmental impact that it could potentially create are among the most significant challenges to its rapid implementation. This publication aims at illustrating the technological, environmental, economic, and policy challenges that interregional HV transmission systems face today in the US, looking specifically at the Clean Line Rock Island project in Iowa.