Microalgal biomass is considered a promising energy feedstock with multifaceted applications in the production of sustainable biofuels, nutraceuticals, and health supplements. Commercial-scale cultivation of microalgae is an indispensable part of the biomass generation process and photobioreactors play a vital role in the efficient production of microalgal biomass in the most profitable way. This chapter presents comprehensive information on the characteristics of microalgae cultivation, as well as the key factors and challenges for the phototrophic process.