Standard way of laboratory utilisation does not meet professional and financial criteria. Rational laboratory use, which in essence means nothing else than seeking the answer to a specific clinical question, must be the basis for a changing approach towards laboratory diagnostics. In order to do that, clinicians need to have access to all the information necessary for right data interpretation, which is usually not the case. The following points are discussed: clinicians have to get acquainted with the preanalytical issues which affect the laboratory result, with analytical and biological variability of any given laboratory parameter, critical difference within longitudinal patient evaluation, as well as with diagnostic specificity and sensitivity which determine the value of a test within certain clinical context. Preanalytical phase comprises all the influences affecting the patient and the specimen and it can have a substantial impact on laboratory values. Biological variability is mainly dependent on homeostatic regulation, and it might thus be considerably high for certain parameters (end products of the metabolism, enzymes). As a consequence, the value of critical difference (absolute value in actual units which reflects a true change in clinical status) might be unexpectedly high. Finally, diagnostic sensitivity and specificity are main determinants of diagnostic performance of any given test and the lack of this information is a frequent cause of inappropriate laboratory use.