Lipid management is an important strategy to prevent cardiovascular disease in patients with and without diabetes mellitus. Although diabetic patients are often characterized by hypertriglyceridemia or mixed dyslipidemia LDL-cholesterol reduction translates best into risk reduction. Therefore the European and American guidelines focus on LDL-reduction using life-style modification, statins, ezetimibe and PCSK9-inhibitors. In patients with diabetes and established cardiovascular disease or additional risk factors LDL-cholesterol should be ≤70 mg/dl (1.8 mmol/l), in all other patients with diabetes the LDL-cholesterol goal is ≤100 mg/dl (2.6 mmol/l). Numerous studies (using statins, ezetimibe and PCSK9-inhibitors) clearly show that lower LDL-cholesterol levels are associated with lower risk without attenuation at very low LDL-levels. Patients at particular high absolute risk (such as patients with peripheral arterial disease or diabetic patients) may benefit particularly from very low LDL-cholesterol levels. Thus, in patients at very high risk achieving very low LDL-cholesterol levels may be of particular benefit. European guidelines also define non-HDL-cholesterol levels as secondary goals which is particularly relevant in patients with mixed dyslipidemia. These goals can be reached either by lowering triglycerides or by further lowering LDL-cholesterol. It should be noted that triglyceride-lowering with fibrates and/or niacin has not been proven successful in outcome trials. Therefore, further lowering of LDL-cholesterol may be the best strategy to also reach non-HDL-cholesterol goals. However, it is unclear in which patients non-HDL goals should be reached (besides LDL-cholesterol goals).