Microbial-based biodiesel is produced by transesterification of lipids extracted from microbial cells, and is considered as a potential replacement of fossil fuel due to its advantages in reducing greenhouse gas emissions. Yarrowia lipolytica is one of the most studied oleaginous yeasts able to produce lipids under some fermentation conditions and is considered as a potential industrial host for biodiesel production. Several approaches have been evaluated to increase the economical attraction of biodiesel production from Y. lipolytica lipids. In this review, we highlighted the different strategies reported in the literature, allowing this yeast to achieve high lipid accumulation. These include metabolic engineering strategies, the use of low-cost effective substrates, and the optimization of the cultivation conditions for higher lipid productivity and less operating cost. We also summarized the most effective cell disruption technologies that improve the extraction efficiencies of lipids from Y. lipolytica.