Although gene therapy strategies are applicable to genetically determined, preferably monogenic disorders, recent advances regarding multifactorial disorders, such as atherosclerosis, are promising. Gene therapy strategies have been developed against genetically determined risk factors, such as familial hypercholesterolemia and familial dysbetalipoproteinemia, as well as to stimulate factors that protect against, or reverse, the disease through overexpression of protective lipoproteins, such as highdensity lipoproteins (HDL). For gene polymorphisms associated with increased risk of atherosclerosis, genetically guided drug therapy (eg, angiotensin-converting enzyme (ACE) inhibitors in patients with DD ACE genotype) is a distinct possibility. Other genetic determinants need to be addressed, eg, hyperhomocysteinemia. Future gene therapy strategies for atherosclerosis will likely evolve in tandem with the emergence and elucidation of individual determinants...