In clinical chemistry today there are often several different methods and instruments in use for the analysis of a particular constituent. When these different methods and instruments are used for careful analysis of the same control specimen, as in assigned value determinations, the assigned values obtained may be significantly different, and these differences may be of clinical importance. In order to determine the reasons for such differences, reference systems or reference points are needed. The reference systems for calibration (calibration materials, standard reference materials) and control (control materials), where the matrices of these different materials must have quite different characteristics, are referred to jointly as reference materials. In order to compare methods, reference methods are needed with known, high reliability. Because of the amount of specimen material needed, the time needed for analysis and the facilities required, reference methods are not suitable for routine analysis. IDeally, standard reference materials are developed first, followed by a definitive method, which is then used to evaluate a candidate reference method. This is currently the case for only a small number of the constituents analyzed in the clinical chemistry laboratory. In this paper the characteristics of the different kinds of reference materials and of reference methods are described. The differences in terminological usage found in the literature are discussed. Limitations of knowledge and technique may necessitate certain compromises, with respect to the ideal characteristics of reference materials and reference methods. Possible compromises are discussed, and the various sources of error associated with them are pointed out. However, these compromises can also lead to improvement in the reliability and comparability of analytical results from different laboratories. As an example of such improvement, the results are presented for assigned value determinations by highly qualified reference laboratories on control specimens for interlaboratory surveys; the decision limits are included and the results are compared with those of the survey participants. Thus various ways are indicated for the use of reference materials and reference methods to improve the reliability and comparability of analytical results, suited to the current state of the art.