Triglyceride-rich lipoproteins deliver fatty acids to tissues for oxidation and for storage. Release of fatty acids from circulating lipoprotein triglycerides is carried out by lipoprotein lipase (LPL), thus LPL serves as a critical gatekeeper of fatty acid uptake into tissues. LPL activity is regulated by a number of extracellular proteins including three members of the angiopoietin-like family of proteins. In this review, we discuss our current understanding of how, where, and when ANGPTL3, ANGPTL4, and ANGPTL8 regulate lipoprotein lipase activity, with a particular emphasis on how these proteins interact with each other to coordinate triglyceride metabolism and fat partitioning.