The theoretically high efficiency and low temperature operation of hydrogen-oxygen fuel cells have motivated them to be the subject of much study since their invention in the 19th century, but their relatively high life cycle costs have kept them as a “solution in search of a problem” for many years. The first problem for which fuel cells presented a truly cost effective solution was that of providing a power source for NASA’s human spaceflight vehicles in the 1960s. NASA thus invested, and continues to invest, in the development of fuel cell power plants for this application. This development program continues to place its highest priorities on requirements for minimum system mass and maximum durability and reliability. These priorities drive fuel cell power plant design decisions at all levels, even that of catalyst support. However, since the mid-1990s, prospective environmental regulations have driven increased governmental and industrial interest in “green power” and “the hydrogen economy.” This has in turn stimulated greatly increased investment in fuel cell development for a variety of commercial applications. This investment is bringing about notable advances in fuel cell technology, but as these development efforts place their highest priority on requirements for minimum life cycle cost and field safety, these advances are yielding design solutions quite different at almost every level from those needed for spacecraft applications. This environment thus presents both opportunities and challenges for NASA’s Human Exploration program.