The production of biofuels from microalgae requires efficient photobioreactors in order to meet the tight constraints of energy efficiency and economic profitability. Current cultivation systems are designed for high-value products rather than for mass production of cheap energy carriers. Future bioreactors will imply innovative solutions in terms of energy efficiency, light and gas transfer or attainable biomass concentration to lower the energy demand and cut down production costs. A new generation of highly developed reactor designs demonstrates the enormous potential of photobioreactors. However, a net energy production with microalgae remains challenging. Therefore, it is essential to review all aspects and production steps for optimization potential. This includes a custom process design according to production organism, desired product and production site. Moreover, the potential of microalgae to synthesize valuable products additionally to the energetic use can be integrated into a production concept as well as waste streams for carbon supply or temperature control.