The multiple drivers of increasing global energy demand, diminishing fossil fuel reserves and the urgent need to mitigate greenhouse gas emissions from non-renewable energy sources have led to a growing international interest in supplementary energy, and invigorated research into alternative and renewable fuel sources. To date, the majority of biofuels are derived from terrestrial crops which compete for freshwater and arable land resources in the face of a rising population lacking food or access to potable water. This means that photosynthetic organisms such as microalgae are a promising alternative, capable of growing in saltwater and a diverse range of environments. Furthermore, the cultivation process can take place on non-arable land, and the accumulated biomass can cleanly generate biofuel precursors. Despite their promise, none of the currently known strains of microalgae are biologically productive enough to produce commercially viable biofuels. At the forefront of this research is the development of 4th generation feedstocks for biofuel production. This development focuses on the use of synthetic biology to produce genetically modified industrial microalgal strains that hyper-accumulate neutral lipids. This review examines the most promising approaches in this rapidly evolving field, for example, direct upregulation of the storage lipid metabolic pathway, shunting of competing pathways such as the starch storage pathway, and improving photosynthetic efficiency. The most recent advances in gene editing technologies are also discussed. Though successful, these individual strategies do not yet offer enough of a biological improvement to achieve commercially viable biofuels, requiring, in our opinion, future research to focus on the combination of strategies to achieve the synergistic boost in lipid yield needed for commercial viability. In this review, we propose a strategy based on this principle which would theoretically increase the lipid yield of Chlamydomonas reinhardtii 10-fold, with minimal effect on growth rate.