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Operations within the Next Generation Air Transportation System (NextGen) will be a source of new complexities and unique challenges for the single pilot. Human factors research and development will be required to ensure safe single-pilot operations. New avionics, the increase in procedural complexity, and the elevated standards for required navigation performance are the source of many issues that need to be identified before they become a threat to safety. This paper presents a taxonomy developed to identify the potential human factors issues that could impact single pilots flying within NextGen. A series of NextGen capabilities, scenarios, and Automatic Dependent Surveillance-Broadcast (ADS-B) applications were extracted from the literature and examined to determine potential single-pilot human factors issues. A priority list was created to emphasize the issues that constitute the biggest threat to single pilots. The implications of the results are discussed in this paper, and recommendations are given for future research.