The unraveling of genetic defects associated with disorders in lipid metabolism has contributed to the understanding of lipoprotein metabolism and the pathophysiological consequences of a particular mutation. The translation, however, of a single genetic defect into the individual's risk of cardiovascular disease and subsequent treatment strategies is an extremely complex issue that involves the identification of multiple additional determinants, including genetic, metabolic and environmental factors. The discovery of these factors, including genetic determinants of drug efficacy, provides insight into the interaction between regulatory systems traditionally thought to be unrelated and may, in the future, lead to a more complete diagnostic and therapeutic appreciation of the individual patient.