Dyslipidemia is an established cardiovascular risk factor in the general population. However, in patients suffering from chronic kidney disease (CKD) this relationship is less clear, and many studies show that low, rather than high, cholesterol levels predict mortality in this patient population. This review presents an overview of the major disorders of lipid metabolism in the course of CKD and their clinical implications. We also discuss the role of genetic determinants predisposing to dyslipidemia, as well as current therapeutic approaches. Finally, the mendelian randomization approach as a novel tool to elucidate the seemingly paradoxical association between hypercholesterolemia and mortality in CKD will be discussed.