Cytoplasmic lipid droplets (LDs) are organelles in which cells store neutral lipids for use as an energy source in times of need, but they also play important roles in the regulation of key metabolic processes. Although LDs are essential for normal cell function, excess accumulation of intracellular lipid is associated with several metabolic diseases, including obesity, type 2 diabetes, and atherosclerosis. The function of LDs is regulated by their associated proteins, including the members of the PAT family: perilipin, adipophilin/adipose differentiation-related protein, tail-interacting protein 47, S3-12, and OXPAT/myocardial LD protein/lipid-storage droplet protein 5. In this review we discuss the PAT proteins in two cardiovascular contexts: 1) in the atherosclerotic vessel wall, where LDs within macrophage foam cells store cholesteryl esters derived from modified lipoproteins, and 2) in the myocardium, where LDs store fatty acids, the major energy substrate for normal heart function, as triglyceride.