?On August 27, 2006, about 0606:35 eastern daylight time, Comair flight 5191, a Bombardier CL-600-2B19, N431CA, crashed during takeoff from Blue Grass Airport, Lexington, Kentucky. The flight crew was instructed to take off from runway 22 but instead lined up the airplane on runway 26 and began the takeoff roll. The airplane ran off the end of the runway and impacted the airport perimeter fence, trees, and terrain. The captain, flight attendant, and 47 passengers were killed, and the first officer received serious injuries. The airplane was destroyed by impact forces and postcrash fire. The flight was operating under the provisions of 14 Code of Federal Regulations Part 121 and was en route to Hartsfield-Jackson Atlanta International Airport, Atlanta, Georgia. Night visual meteorological conditions prevailed at the time of the accident. The safety issues discussed in this report focus on the need for (1) improved flight deck procedures, (2) the implementation of cockpit moving map displays or cockpit runway alerting systems, (3) improved airport surface marking standards, and (4) ATC policy changes in the areas of taxi and takeoff clearances and task prioritization. Safety recommendations concerning these issues are addressed to the FAA.