Lipid profile screening is crucial for the prevention, evaluation and treatment of cardiovascular (CV) disease (CVD). Small dense low-density lipoprotein-cholesterol (sdLDL-C) is an emerging biomarker associated with CVD and several comorbidities. The aim of this literature review is to discuss the potential importance of sdLDL-C as a surrogate biomarker for managing CVD by explaining its pathophysiology and promising treatments. The current synthesis demonstrates the impact of sdLDL-C on CV ailments, which are related to arterial pathologies and dysregulated lipid profiles. Several drug classes used for the treatment of dyslipidemia decrease the sdLDL-C concentrations. For instance, statins, fibrates, ezetimibe, nicotinic acid, resin and orlistat are pharmacological sdLDL-C-lowering agents. Regarding nutritional strategies, simple carbohydrate types, such as fructose, are common in Western diets and should be reduced or avoided due to their potential in increasing synthesis of sdLDL-C subclasses. Dairy products, avocado, pistachios, soy-based diet (except for hydrogenated soybean oil) and corn oil seem to be suitable food choices for a therapeutic diet aiming to control sdLDL-C concentrations. However, thus far dietary supplementation with omega-3 fatty acids is unsubstantiated for decreasing sdLDL-C concentration. In conclusion, coupled with the traditional lipid profile, measurement or even the estimation of sdLDL-C as a routine screening should be encouraged, whereas more insights into the control of sdLDL-C are imperative. Appropriate clinical reference ranges for sdLDL-C are also needed.Copyright © 2020. Published by Elsevier Inc.