Dyslipidemia should be monitored regularly in diabetes mellitus and the assessment should include the measurement of total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations. More detailed investigations may be required if a primary hyperlipoproteinemia is suspected and other causes of secondary hyperlipidemia should be considered. Several physiological factors cause variation in serum lipid concentrations, including age, sex, the menstrual cycle, and diet. Posture, venepuncture technique, concomitant medication, and clinical conditions other than diabetes mellitus also affect lipid levels. This chapter will consider the investigations that are used widely in clinical practice and sources of variation in lipoprotein metabolism.