Microalgae biotechnology has taken the world by storm. However, despite its great potential promise, it still cannot be considered a fully consolidated technology due to a crucial challenge: the low rates of biomass productivity. To overcome this hurdle, photobioreactors have been developed as an innovative solution, promising to increase the efficiency of microalgae cultures by providing optimized conditions. However, the results obtained with these systems do not always meet initial expectations, and their large-scale implementation faces complex technical challenges. In light of this, the present review addresses the main aspects related to the design and engineering of photobioreactors, highlighting their potentialities and limitations in overcoming the critical challenges of microalgal biotechnology. Furthermore, we discuss the current technological readiness level and the commercial readiness index of microalgae-based bioproducts from the perspective of industrial-scale production.