The limitations of post mortem detection of early myocardial infarction by hematoxylin and eosin staining stimulated a search for the development of improved diagnostic methods based on biochemical and morphologic changes. Methods used and/or investigated included electron microscopic examination, gross and microscopic histochemical stains (tetrazolium salts, phosphotungstic acid-hematoxylin, trichrome, periodic acid-Schiff, hematoxylin-basic fuchsin-picric acid), fluorescence, immunohistochemical techniques, and chemical analysis of pericardial fluid. This practical review, designed for both forensic and hospital-based autopsy pathologists, examines the methods available for post mortem diagnosis of myocardial infarction for cases in which death might have occurred before the evolution of changes detectable by hematoxylin and eosin staining. The status and potential usefulness of each adjunct to classical morphologic examination is summarized. Recent developments are highlighted, including the possibility of using apoptosis as a marker for acute ischemic injury.