The general trend of microscopical investigation in biology from the 1950s to the early 1970s was towards obtaining structural information. This goal initially was met using heavy metal and/or aldehyde fixatives, room temperature dehydration with polar organic liquids, embedding with epoxy and acrylate resins, and thin sectioning at room temperature. By the mid 1970s, a perceptible change occurred in the direction of both light and analytical electron microscopy towards investigation of the chemical reactivity and composition of structures made visible with increasingly better spatial resolution for light and electron microscopes. During the past 25 years there have been considerable innovations in microanalytical techniques, including analytical electron and x-ray microscopy and microanalysis, secondary ion mass spectrometry, laser microprobe mass analysis, the scanning probe microscopies, and confocal/multi-photon microscopy. In addition, cryopreservation and the development of chromophores for visualization of molecular and ionic sites within individual living cells as well as membranes have redefined the goal of microscopical preservation: to stabilize cell structure and composition as they exist in the living state.