While a number of pathways for the catabolism and tissue delivery of intravenous lipid emulsions are shared by chylomicrons, there are also important differences. The introduction of medium-chain triglycerides (MCTs) and n-3 fatty acid-containing fish oils into lipid emulsions has marked effects on their clearance from the bloodstream and the delivery of fatty acids to organs, and it involves pathways different from those required for n-6 fatty acid-rich soybean oil-based particles. 1) Multiple pathways are responsible for the blood clearance and tissue uptake of MCT- and fish oil-containing emulsions. 2) Both human and animal model-based studies were needed to define these ‘classical' and ‘novel' pathways, which are respectively similar to and different from those involved in chylomicron clearance. 3) n-3 fatty acid-rich triglycerides and MCTs provide new opportunities for lipid emulsions to act as metabolic and immune modulators.