Despite extensive research, it has not yet been determined whether triglycerides represent an independent risk factor for coronary heart disease (CHD). The association has been obscured by imprecision in triglyceride measurements, individual variability, and complex interactions between triglycerides and other lipid-nonlipid parameters. Recent large-scale epidemiologic data indicate that elevated fasting triglycerides represent a useful marker for risk of coronary heart disease. The strong interrelationships of triglyceride level, high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) particle size with CHD risk suggest a metabolic interaction between the triglyceriderich and cholesterol ester-rich lipoproteins in increasing risk of myocardial infarction. Limited data from clinical trials suggest that intervention with agents that lower triglycerides and raise HDL tend to reduce event rates among those with elevated and normal LDL levels. Many important issues defining the role of triglycerides in the primary and secondary prevention of CHD need further evaluation. These issues include the degree of risk associated with high triglyceride levels in various age, gender, racial, and ethnic subgroups, and the prognostic significance of postprandial versus fasting triglyceride levels. Further, primary and secondary intervention trials that more specifically address the clinical benefit of reducing triglyceride levels are warranted. Ultimately, screening and treatment guidelines may have to be modified to allow greater focus on fasting-triglyceride levels. Although current guidelines do not mandate screening for elevated triglyceride levels in the general population, obtaining triglyceride levels in those with known CHD or with other risk factors can provide valuable prognostic information and therefore be of aid in therapeutic decisions.