To mitigate global warming caused by burning fossil fuels, a renewable energy source available in large quantity is urgently required. We are proposing large-scale photobiological H2 production by mariculture-raised cyanobacteria where the microbes capture part of the huge amount of solar energy received on earth’s surface and use water as the source of electrons to reduce protons. The H2 production system is based on photosynthetic and nitrogenase activities of cyanobacteria, using uptake hydrogenase mutants that can accumulate H2 for extended periods even in the presence of evolved O2. This review summarizes our efforts to improve the rate of photobiological H2 production through genetic engineering. The challenges yet to be overcome to further increase the conversion efficiency of solar energy to H2 also are discussed.