The failure of the New Orleans regional flood protection systems, and the resultant catastrophic flooding of much of New Orleans during Hurricane Katrina, represents the most costly failure of an engineered system in U.S. history. This paper presents an overview of the principal events that unfolded in the central portion of the New Orleans metropolitan region during this hurricane, and addresses the levee failures and breaches that occurred along the east-west trending section of the shared Gulf Intracoastal Waterway/Mississippi River Gulf Outlet channel, and along the Inner Harbor Navigation Channel, that affected the New Orleans East, the St. Bernard Parish, and the Lower Ninth Ward protected basins. The emphasis in this paper is on geotechnical lessons, and also broader lessons with regard to the design, implementation, operation, and maintenance of major flood protection systems. Significant lessons learned here in the central region include: (1) the need for regional-scale flood protection systems to perform as systems, with the various components meshing well together in a mutually complementary manner; (2) the importance of considering all potential failure modes in the engineering design and evaluation of these complex systems; and (3) the problems inherent in the construction of major regional systems over extended periods of multiple decades. These are important lessons, as they are applicable to other regional flood protection systems in other areas of the United States, and throughout much of the world.