The storage of fatty acids and fatty alcohols in the form of neutral lipids such as triacylglycerol (TAG), cholesteryl ester (CE), and wax ester (WE) serves to provide reservoirs for membrane formation and maintenance, lipoprotein trafficking, lipid detoxification, evaporation barriers, and fuel in times of stress or nutrient deprivation. This ancient process likely originated in actinomycetes and has persisted in eukaryotes, albeit by different molecular mechanisms. A surfeit of neutral lipids is strongly, perhaps causally, related to several human diseases such as diabetes mellitus, obesity, atherosclerosis and nonalcoholic fatty liver disease. Therefore, understanding the metabolic pathways of neutral lipid synthesis and the roles of the enzymes involved may facilitate the development of new therapeutic interventions for these syndromes.