Aspects of metabolic control theory and experiments from metabolic biochemistry are reviewed in order to deduce the circumstances in which experimental studies involving metabolomics have the greatest chance of success. It is concluded that metabolic changes effected mainly through a single enzyme are those most likely to lead to large changes in metabolite concentrations. Metabolic changes brought about through signal transduction mechanisms will tend to result in relatively much smaller adjustments in metabolite concentrations, whilst allowing significant changes in metabolic rates.