Introduction: Atherosclerotic cardiovascular disease (ASCVD) is the main cause of morbidity and mortality worldwide. Dyslipidemia, in particular elevation of LDL-cholesterol levels (LDL-C), is one of the major cardiovascular risk factors and is characterized by high prevalence and independent unfavorable impact on cardiovascular prognosis; however, because of its asymptomatic course, it often remains undiagnosed. Strategies aimed at early identification of subjects with elevated LDL-C levels may allow early intervention, preventing ASCVD development. Areas covered: The purpose of this review is to summarize the recommendations of current guidelines by leading scientific authorities on the pros and cons of lipid profile screening programs. Expert opinion: Systematic assessment of LDL-C levels as part of global cardiovascular risk assessment in all adults is a cornerstone of ASCVD risk prevention. In young adults, adolescents, and children, selective lipid profile screening may be useful to reduce the impact of high cholesterol levels on ASCVD risk in the presence of specific conditions including either family history of early ASCVD or multiple concomitant cardiovascular risk factors. Cascade screening for family members of individuals diagnosed with familial hypercholesterolemia (FH) may be also of great clinical impact. Further evidence is needed to evaluate the cost/benefit ratio of systematic assessment of lipid profile in children, adolescents, and young adults.