This review surveys the emergence of electron probe X-ray microanalysis as a quantitative method for measuring the chemical elements in situ. The extension of the method to the biological sciences under the influence of Ted Hall is reviewed. Some classical experiments by Hall and his colleagues in Cambridge, UK, previously unpublished, are described; as are some of the earliest quantitative results from the cryo-sections obtained in Cambridge and elsewhere. The progress of the methodology is critically evaluated from the earliest starts to the present state of the art. Particular attention has been focused on the application of the method in providing fresh insights into the role of ions in cell and tissue physiology and pathology. A comprehensive list of references is included for a further pursuit of the topics by the interested reader.