On January 14, 2004, the President of the United States announced a new and exciting direction for NASA's future with his space exploration initiative. This new policy includes the safe return to flight of the Space Shuttle in order to complete the assembly of the Space Station by the end of this decade and to meet our international obligations with the International Space Station. At that time the Space Shuttle fleet would be retired. In addition, the Orbital Space Plane program was cancelled and replaced by a new Crew Exploration Vehicle program, which will serve as both a crew transport to low Earth orbit, and beyond. The key element of the new policy is a return to the Moon by 2020. The expeditions to the Moon will be used to gain experience and knowledge to serve as a foundation for human exploration to Mars, and elsewhere in our solar system. But before we get to the Moon, we are already establishing a foundation of experience, knowledge, and lessons learned about long duration human space flight operations with the International Space Station, which has been in low Earth orbit for over six years. This paper highlights some of the lessons learned during the construction and operation of the Space Station that will help to take us to the Moon, Mars, and beyond.