Familial hypercholesterolemia is characterized by high LDL cholesterol and an elevated risk to develop coronary heart disease. Mutations in LDL receptor-mediated cholesterol uptake are the main cause of familial hypercholesterolemia. However, multiple mutations in various other genes are also associated with high LDL cholesterol and even familial hypercholesterolemia. Thus, pharmaceuticals that target these genes and proteins might be attractive treatment options to reduce LDL cholesterol. This review provides an overview of the recent developments and clinical testing of such pharmaceuticals.