Several lines of evidence have demonstrated that increased plasma cholesterol plays a primary role in the etiology of atherosclerosis and ischemic heart disease (IHD). Our ability to manage IHD adequately based on plasma cholesterol or low density lipoprotein (LDL) cholesterol concentrations is challenged, however, by evidence suggesting that a significant proportion of individuals with IHD or who will eventually develop IHD have desirable cholesterol concentrations. These observations have generated much interest in the scientific community, with the resultant identification of new metabolic risk factors that may help, in the future, to improve our ability to reduce the risk of IHD adequately. This review presents evidence that hypertriglyceridemia, particularly when associated with reduced high density lipoprotein (HDL) cholesterol concentrations and abdominal or visceral obesity, is a highly atherogenic phenotype, one that requires aggressive risk reduction management. Hypertriglyceridemia is frequently associated with elevated plasma apolipoprotein B concentrations, with states of hyperinsulinemia or insulin resistance and with small, dense LDL particles, which may all contribute to increase the risk of IHD further. This evidence suggests that a therapeutic strategy based on the assessment of plasma triglyceride concentrations, along with HDL cholesterol levels and abdominal obesity, may be a cost effective approach to assessing the high atherogenic risk of visceral obesity and insulin resistance. We can no longer afford to focus our attention exclusively on the detection and management of elevated LDL cholesterol concentrations, and need to adopt comprehensive risk reduction strategies in order to lower the incidence of IHD.