Lipoprotein lipase is an important regulator of lipid and lipoprotein metabolism. It also contributes to the lipid and energy metabolism of different tissues in varying ways. Although the synthesis, manner of secretion, and mechanism of endothelial binding of lipoprotein lipase appear similar in all tissues, the factors that control gene expression and posttranslational events related to processing vary from tissue to tissue. The actual molecular events that determine this tissue specificity are not yet understood. In the future, however, it may be possible to stimulate or inhibit the activity of lipoprotein lipase in specific tissues and to alter metabolic processes so as to improve the quality and length of life in patients with metabolic diseases such as hypertriglyceridemia, HDL2 deficiency, and obesity.