Diagnostic electron microscopy (DEM) has conceptual predecessors â€" the application of the sense of vision and of light microscopy in medicine. The evolvement of DEM and the role of its two branches - histopathology and rapid negative-contrast DEM - are described in this review, with a focus on the latter. By its resolving power of 2 nm in praxi, DEM is able to visualize all kinds of pathogens, bacteria, parasites, even the smallest viruses. In contrast to other laboratory diagnostic methods, DEM excels by speed and "open view". All structures on the support grid can be assigned directly by "pattern recognition" of their fine structure to a specific family of agents. The morphology-based "catch-all" diagnosis can be decisive as a differential diagnosis and will help as a preliminary diagnosis to select and apply proper diagnostic tools for typing of the observed agent. Based on two case reports, the advantages and possible pitfalls of DEM are exemplified and hints are given to make DEM reliable and effective. Finally the role of DEM in medicine and the wider fields of life sciences are described together with the organizational conditions to guarantee its future in laboratory diagnostics.