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Securing food, energy, and raw materials for a growing population is one of the most significant challenges of our century. Algae play a central role as an alternative to plants. Wastewater and flue gas can secure nutrients and CO 2 for carbon fixation. Unfortunately, algae domestication is necessary to enhance biomass production and reduce cultivation costs. Nannochloropsis spp. have increased in popularity among microalgae due to their ability to accumulate high amounts of lipids, including PUFAs. Recently, the interest in the use of Nannochloropsis spp. as a green bio-factory for producing high-value products increased proportionally to the advances of synthetic biology and genetic tools in these species. In this review, we summarized the state of the art of current nuclear genetic manipulation techniques and a few examples of their application. The industrial use of Nannochloropsis spp. has not been feasible yet, but genetic tools can finally lead to exploiting this full-of-potential microalga.