Familial hypercholesterolemia is a genetic disorder associated with elevated LDL-cholesterol and high lifetime cardiovascular risk. Both clinical and molecular cascade screening programs have been implemented to increase early definition and treatment. In this systematic review, we discuss the main issues found in 65 different articles related to cascade screening and familial hypercholesterolemia, covering a range of topics including different types/strategies, considerations both positive and negative regarding cascade screening in general and associated with the different strategies, cost and coverage consideration, direct and indirect contact with patients, public policy around life insurance and doctor -patient confidentiality, the "right to know," and public health concerns regarding familial hypercholesterolemia.J Atheroscler Thromb, 2015; 22: 869-880.