The concept of in-situ resource utilization (ISRU) has become an important part of current architectures for both a return to the Moon and the eventual human exploration of Mars. The ability to manufacture life support components and propellants from local resources will enable future human exploration of our solar system. ORBITEC has conducted a NIACsponsored study of an overall system architecture for a self-sustaining lunar colony (SSLC). A self-sustaining colony would be able to survive without any supplies or resources from Earth for an extended period of time. The design of a self-sustaining architecture appears to be feasible and represents an attractive alternative to what would be a regular Earth-supported lunar colony. The SSLC has several benefits, such as reducing the operating costs of the colony and reducing the risks of operating the colony remotely. The establishment of SSLC is necessary to drive new innovative approaches/ developments that would ultimately support a much lower cost and highly-survivable human colonization of the Moon, Mars, and other bodies in the solar system. Once established, the SSLC will implement many innovative applications for the production of needed structures and commodities from lunar materials. This paper outlines the vital role of ISRU in the system architecture of the SSLC.