The current burden on fossil-derived chemicals and fuels combined with the rapidly increasing global population has led to a crucial need to develop renewable and sustainable sources of chemicals and biofuels. Photoautotrophic microorganisms, including cyanobacteria and microalgae, have garnered a great deal of attention for their capability to produce these chemicals from carbon dioxide, mineralized water, and solar energy. While there have been substantial amounts of research directed at scaling-up production from these microorganisms, several factors have proven difficult to overcome, including high costs associated with cultivation, photobioreactor construction, and artificial lighting. Decreasing these costs will substantially increase the economic feasibility of these production processes. Thus, the purpose of this review is to describe various photobioreactor designs, and then provide an overview on lighting systems, mixing, gas transfer, and the hydrodynamics of bubbles. These factors must be considered when the goal of a production process is economic feasibility. Targets for improving microalgae and cyanobacteria cultivation media, including water reduction strategies will also be described. As fossil fuel reserves continue to be depleted and the world population continues to increase, it is imperative that renewable chemical and biofuel production processes be developed toward becoming economically feasible. Thus, it is essential that future research is directed toward improving these processes. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:811-827, 2018.