The dynamic behavior of cells is a consequence of the coordinated and elaborate interactions between complexes of macromolecules that constitute their formed structures or organelles. Live-cell imaging and high-resolution determination of the location of nucleic acids, proteins, metabolites, and ions can now be made within subcellular domains down to the molecular level, revealing the important information required to understand complex cellular functioning. Light and electron microscopic methods have proved extremely powerful in providing information about cells, and techniques such as immunolabeling have been applied successfully to identify molecules in situ. Recently, developments in recombinant methods of modern molecular biology and synthetic chemistry have lead to new probes and targeting techniques for these correlated modalities. Here we review whole cell, organelle, and protein labeling methods for correlated observations in the spatial domains of both light and electron microscopy.