There is a need for revisiting theoretical concepts and practical applications of conventional population-based reference values to make for better clinical use of laboratory data. Knowledge of the underlying biological variation of quantities examined in medical laboratories is vital to understanding the proper generation and application of traditional population-based reference values. Appreciation of the biological changes that occur over the span of life is a necessary prerequisite to deciding whether stratification of reference values according to age is likely to be necessary. Knowledge of the detail of predictable biological cyclical rhythms is required for correct clinical interpretation of laboratory data and appropriate collection of specimens at times relevant to the clinical purpose. Quantitative data on inherent within- and between-subject biological components of variation have shown the marked individuality of most quantities of interest in laboratory medicine. This individuality casts light on why examinations are not generally very successfully applied in population screening or case-finding. Consideration of individuality demonstrates why stratification of reference values is often very advantageous. Individuality provides an indisputable argument for better use of individual specific reference values.