The phenomenon of fluorescence is used in microscopy to contrast subcellular structures and, in conjunction with immunohistochemistry, allows for precise localization of subcellular components. As many biological specimens appear colorless and transparent when viewed with a light microscope, the contrast in the image must be increased to distinguish fine structures from each other. This can be achieved either by optical contrast methods such as phase contrast, differential interference contrast (DIC), dark field, or simple polarization. Alternatively, contrast can also be achieved through specific staining of the fine structures in the examined samples. This chapter introduces the application and significance of fluorescence microscopy.