Expense, high drug dose, and low compliance to strict dietary therapies are current issues surrounding modern drug- and diet-based lipid-lowering approaches. Furthermore, variable patient outcomes and suboptimal response to both drug and diet therapies are increasingly evident. Therefore, the question arises as to whether more emphasis should be placed on combination diet/drug therapies to reduce cholesterol levels in patients who respond suboptimally to diet and drug monotherapies. Although considerable research has explored multidrug combination therapies, combination drug/diet therapies receive less attention. However, combined drug/diet approaches may reduce the number of drug prescriptions, the progressive increase in "optimal" drug dosage, and costs associated with pharmaceutical disease management. Future research priorities in drug/diet therapeutic approaches should not only emphasize the discovery of novel combinations but also should address potential safety issues prior to wide-scale acceptance in clinical practice. Accordingly, this review will assess current limitations associated with both drug and diet lipid-lowering therapies and explore the potential of combination drug/diet therapies in the treatment of dyslipidemia.