Histochemistry has an interesting history, extending back to ancient times, in some ways. Man has long had a desire to understand the workings of the human body and the roles that various "humors" or chemicals have in those processes. This review traces the evolution of histochemistry as an investigative and diagnostic discipline, beginning with the efforts of medicinal chemists and extending through a period in which histology was increasingly paired with biochemistry. Those developments served as the underpinnings for an eventual marriage of microscopy, chemistry, immunology, and molecular biology, as realized in the current practice of anatomical pathology.