The endemic increase in lipid-associated disorders such as obesity and type 2 diabetes mellitus has placed triacylglycerol metabolism and its associated organelle, lipid droplets, in the spotlight of biomedical research. Key enzymes of triacylglycerol metabolism are structurally and functionally conserved between yeast and mammalian cells, and studies in yeast have contributed significantly to the understanding of their biological function(s). Based on these similarities, studies performed in yeast may provide further significant mechanistic insight into the molecular basis of triacylglycerol homeostasis and its important physiological roles in healthy and diseased cells.