The growing demand for sustainable production of high-value compounds, such as biofuels, lipids, and pigments like carotenoids and phycobilin, has become the subject of numerous investigations. Furthermore, this fact has led to the exploration of re-newable methods utilizing microalgae as feedstock to mitigate the challenges associ-ated with producing these valuable compounds. Nevertheless, despite the numerous advantages of microalgae, the development of a microalgal biorefinery that employs sustainable, environmentally friendly, and economically efficient technologies remains a necessity. To address this challenge, the bio-flocculation process and more specially the self-flocculation ability, is presented as a cost-effective and energy-efficient solu-tion. This method is as easy and effective as chemical flocculation, which is applied at industrial scale, however in contrast, it is sustainable and cost-effective as no costs are involved for pre-treatment of the biomass for oil extraction and for pre-treatment of the medium before it can be re-used. In addition, microalgae possess molecular tools that would allow increasing the efficiency of these processes. In the present review, we summarize microalgal harvesting technologies, with a particular focus on bio- and self-flocculation processes and identify the improvement technologies that could en-hance the production of high added-value compounds while simultaneously reducing costs in microalgae biorefinery.