The combination of electron microscopy with transmitted light microscopy (termed correlative light and electron microscopy; CLEM) has been employed for decades to generate molecular identification that can be visualized by a dark, electron-dense precipitate. Merging fluorescence and electron microscopy has proven to be far more difficult, but recent technological advances have enabled the study of biological specimens at high resolution through the introduction of fluorescent probes that are capable of generating contrast for electron microscopy. Among the new reagents available for these studies are genetically-encoded fluorescent proteins and hybrid systems that merge synthetic fluorophores with targeting proteins in living cells. Quantum dots and plant phototropins are also emerging as candidates for CLEM assays.