First, we will review the major episodes of the initial clinical investigations on lipoproteins. They were carried out in the 1950s, decade of the expansion of Biochemistry. Gofman and his colleagues, at Berkeley, established the power and versatility of the ultracentrifugation method to study the serum lipoproteins. This research group identified Low Density Lipoprotein cholesterol, rather than generic cholesterol as the atherogenic agent. In 1955, Havel et al. at Bethesda, reported a simpler method for the separation of serum lipoproteins by preparative ultracentrifugation, which permitted chemical analysis of defined fractions. However, there was an obvious need for a technique to undertake a screening of a population because the epidemiological Framingham Study, started in 1946, had confirmed serum cholesterol levels as a major risk factor of atherosclerosis. In 1967, Fredrickson et al. applying electrophoresis methods to the separation of lipoproteins developed a classification of lipoprotein disorders, which was somewhat controversial, but it is still a reference. Alaupovic, pursuing his apolipoprotein studies, introduced the ABC nomenclature, the one in use today. In 1973, Brown and Goldstein described the LDL receptor and its function on regulating cholesterol homeostasis, laying the foundations of a classification of hyperlipoproteinemias on a genetic basis. Then, we will review the genetic basis of lipoprotein disorders, through the work of several research groups, studying, mainly, mutations leading to hypercholesterolemias; most hypertrygliceridemias are not well defined in genetic terms.