All articles assessing adherence to hypolipidemic drugs were reviewed and categorized by patient population (clinical trial, unselected) and reported as rates of nonadherence and discontinuation. Overall, levels of discontinuation reported in clinical trials (6–31%) and lipid clinics (2–38%) are similar, with unselected populations consistently reporting higher rates (15–78%). Rates of nonadherence in clinical trials and lipid clinics also are comparable, with unselected populations having the highest rates. Across all settings, rates of discontinuation and nonadherence are consistently reported to be poorer with resins and niacin than with hydroxy-6-methylglutamate coenzyme A reductase inhibitors. Adherence to hypolipidemic agents appears to decrease in parallel with level of follow-up. Data evaluating mechanisms of poor adherence are limited. While the search for new, efficacious therapies must continue, efforts focused on improving adherence to proven therapy may have a greater overall impact on health than any single new agent.