Although microalgae are a promising biobased feedstock, industrial scale production is still far off. To enhance the economic viability of large-scale microalgae processes, all biomass components need to be valorized, requiring a multi-product biorefinery. However, this concept is still too expensive. Typically, downstream processing of industrial biotechnological bulk products accounts for 20-40% of the total production costs, while for a microalgae multi-product biorefinery the costs are substantially higher (50-60%). These costs are high due to the lack of appropriate and mild technologies to access the different product fractions such as proteins, carbohydrates, and lipids. To reduce the costs, simplified processes need to be developed for the main unit operations including harvesting, cell disruption, extraction, and possibly fractionation. A multi-product biorefinery is essential to make microalgal production of bulk commodities economically feasible.Large-scale cultivation using closed photobioreactors makes microalgal harvesting a smaller economic hurdle in a multi-product biorefinery.Techno-economic scenario studies show that a current multi-product biorefinery requiring multiple unit operations is complex and therefore too expensive.Process simplification can be accomplished by reducing the number of unit operations (e.g., by integrating unit operations or by avoiding auxiliaries in the process chain), making a multi-product biorefinery economically feasible.