Background: Coronary heart disease (CHD) is the major cause of death in the western world and biochemical markers have been used to identify those individuals who are at increased risk. Although numerous markers have been considered, only total, low-density lipoprotein (LDL), and high-density lipoprotein cholesterol, triglyceride and C-reactive protein (CRP) have been recommended for assessing CHD risk in routine clinical practice. Methods: Specific performance goals have been established for the lipid markers and for the measurement of CRP considering both some significant pre-analytical and analytical issues which could affect the quality of their measurements. Results: The target for quality specifications for LDL-C with the reference method are CV ≤4% and bias ≤4%. Regarding the measurement of CRP, total imprecision should be <10% across the linear range of the assay and the analytical sensitivity may allow a reliable measurement at values lower than 0.3 mg/l. Conclusions: Although national guidelines do exist for LDL-C measurement, additional studies are needed to better characterize the performances of routine methods. As more data are available for CRP, guidelines for its measurement will be soon developed.