Marine macroalgae have been used as an efficient feedstock to produce value-added products with several applications. Owing to the high demand for seaweed, novel techniques for intensive production have increased over the past decade. Marine macroalgae are mainly cultivated in sea- or land-based systems such as open tanks or ponds. However, the traditional open systems for the cultivation of macroalgae face challenges such as environmental variability, contamination, and scalability issues; photobioreactor (PBR) provides an efficient controlled and scalable alternative that enhances productivity and ensures a high-quality output. Hence, depending upon the downstream application, for instance, direct food, the macroalgal species need to be cultivated under controlled conditions. Furthermore, PBRs allow for the precise cultivation and harvesting of macroalgae to produce bioactive compounds such as anti-oxidants and anti-microbial or anti-inflammatory agents for pharmaceutical and nutraceutical applications. This controlled environment ensures high purity and potency which is essential for developing new drugs and health supplements. In such a way, these systems can also increase the bio-security and predictable production outcome in terms of both quantity and quality of the overall production of seaweeds. However, the macroalgae production in PBRs is relatively unexplored compared to the microalgae. This chapter gives a brief idea regarding the PBR-based cultivation of macroalgae, different types of PBRs generally used for macroalgae cultivation, factors affecting macroalgae production in PBRs, and strategies to enhance the economic feasibility of seaweed cultivation in PBRs.