This chapter addresses major aspects in the design and scale-up of photobioreactors (PBRs) for hydrogen production, and provides guidelines for optimal process design. Light-driven H2 production is a promising, sustainable process, especially when using the microalga, Chlamydomonas reinhardtii. With present technology, the best strategy is to separate biomass growth from H2 evolution, with H2 production enhanced by sulfur starvation. In addition to optimizing the biological system, careful design and successful operation of the PBRs are of critical importance. Therefore, an optimal, tubular PBR design for the production of C. reinhardtii as the first step is considered, followed by H2 production in either tubular or flat panel PBRs as the second step. Based on available knowledge, the performance of a pilot facility for the continuous production of H2 by the two-step strategy is analyzed, and tubular PBRs are compared with flat panel PBRs. In this way, the potential for light-driven H2 production is evaluated, and major bottlenecks for the large-scale implementation of this technology are identified.