This publication is organized in an exceptional way: Each chapter introduces several completed clinical trials and provides the original conclusions and discussions of the results. The authors then contribute their own comments and interpretations of the findings, challenging the prevailing belief that serum cholesterol is a mediator of disease which is increased by eating saturated fats and decreased by eating polyunsaturated fats. They argue that upon closer scrutiny, the diet recommendations based on the cholesterol hypothesis are essentially ineffective in reducing serum cholesterol levels in the long run. Instead, it is proposed that traditional cholesterol biomarkers are of different significance in short- and long-term interventions due to the feedback control mechanisms in the body. Even more important, the association of high serum cholesterol values with high coronary heart disease mortality is not consistent when different populations are compared: This mortality rate may simply reflect the incidence and severity of familial hypercholesterolemia cases. This agrees with the observation that higher serum cholesterol values associate with lower cancer and all-cause mortalities in populations with a low relative proportion of this disorder. Thus, there seems to be no benefit of limiting dietary cholesterol intake or lowering serum cholesterol values below a certain limit. Moreover, evidence has been found that the health risk results from high intakes of calories, aggravated by an unbalanced intake of omega6/omega3 polyunsaturated fats. Based on the reviewed data, new directions of lipid nutrition are recommended for the primary and secondary prevention of coronary heart disease, cancer and all-cause deaths, which will likely revolutionize current dietary practice.