While most modern commercial airplanes are flown with two pilots, long haul flight operations require augmented flight crews. The normal crew complement conducts the takeoff, climb-out and initial en route segments, additional pilots are on-board. These 'relief' pilots will be rested and ready to take over the flying duties later in the flight. Flight duty times and pre- and post-flight rest requirements currently require multiple flight crews per airplane in order to maximize utilization of the airplane. Advances in intelligent systems, airspace modernization, human factors, and data links are raising the possibility of safely and efficiently operating commercial airplanes with reduced flight crews. As applied to long haul commercial flights, such Reduced Crew Operations (RCO) concepts may include periods of flight where there is only one pilot in the cockpit while other pilot(s) are taking prescribed rest periods. In the RCO concept, the normal flight crew complement (for example, captain and first officer) are in the cockpit for critical flight phases such as takeoff and landing and then alternate flying and resting during cruise. In the event of abnormal operations or an in-flight emergency, the resting pilot can be alerted and called to the flight deck. This paper examines the operational and regulation aspects of Reduced Crew Operations. An impact analysis of the applicable US Federal Aviation Regulations, particularly Part 117 Flight and Duty Limitations and Rest Requirements: Flight Crew Members, and Part 121 Operating Requirements: Domestic, Flag, and Supplemental Operations is presented. This paper provides a summary of the research into RCO concept of operations, including research jointly conducted by NASA and Rockwell Collins. Based on the regulation impacts and the studies, this paper identifies the present operational, procedural, and technical challenges that must be addressed to safely implement Reduced Crew Operations.