Purpose of Review <p>This paper reviews the existing literature supporting a role for fatty acid ethanolamides including oleoylethanolamide and palmitoylethanolamide in regulating cholesterol and triglyceride metabolism and the mechanisms underlying these effects.</p> Recent Findings <p>Deletion of various fatty acid ethanolamide biosynthesis genes in cellular models and small animal models have provided additional evidence that endogenous biosynthesis of fatty acid ethanolamides regulates cholesterol and triglyceride metabolism, while new clinical trials using oleoylethanolamide and palmitoylethanolamide support their therapeutic potential to normalize lipid levels in individuals with cardiometabolic disease.</p> Summary <p>Fatty acid ethanolamides are biosynthesized in the intestine, liver, and adipose tissue in response to metabolic stimuli like fasting and feeding. These fatty acid ethanolamides then act via receptors including PPARα, GPR119, and GPR55 to regulate cholesterol and triglyceride levels and promote the resolution of inflammation, thereby protecting against cardiometabolic diseases including metabolic-dysfunction associated steatotic liver disease and atherosclerotic cardiovascular disease. </p> Graphical Abstract <p></p>