This chapter introduces the multi-agent paradigm and presents concepts and approaches related to multi-agent systems and paradigm-inspired popular research topics such as grid computing, intelligent swarms, sensor networks, service-oriented computing, cloud computing and autonomic computing. Additionally, the chapter reflects the authors' experience and presents a review of the NASA multi-agent applications of ground control and space-exploration systems. The Multi-Agent Systems approach helps NASA systems deal efficiently with huge amounts of data and to perform unmanned tasks in deep space where single monolith spacecraft are impractical.