Familial hypercholesterolaemia (FH) is a genetic disease in which low-density lipoproteins are defectively removed from plasma as a result of mutations that impair the function either of the LDL receptor or of the apolipoprotein B. The consequences are an elevated concentration of LDL-cholesterol and the early occurrence of cardiovascular diseases. Although FH is well understood, it remains a diagnostic challenge for the clinician. Differentiating FH from other causes of hypercholesterolaemia has, however, important clinical and therapeutic implications: FH being associated with early and severe cardiovascular risk, the plasma LDL-cholesterol must be lowered as drastically and as early as possible; because FH is a dominantly inherited disorder, family members need to be screened and counseled. Prevalence, morbidity and genetic characterization of FH have never been explored in our country. Through our experience of large-scale screening of LDL-receptor and Apo B amongst suspected individuals, we are beginning to understand the molecular spectrum of FH in Belgium. Furthermore, using the large collection of clinical data accumulated amongst patients with genetically ascertained FH, we have attempted to establish specific and sensible diagnostic criteria useful and feasible in routine medical practice.