The development of methods to detect and identify biomolecules has been motivated by the ability to improve the study of molecular structure and interactions.  Before the advent of fluorescent labeling, radioisotopes were used to detect and identify molecular compounds.  Since then, safer methods have been developed that involve the use of fluorescent dyes or fluorescent proteins as tags or probes as a means to label and identify biomolecules.  Although fluorescent tagging in this regard has only been recently utilized, the discovery of fluorescence has been around for a much longer time.
Sir George Stokes developed the Stokes Law of Fluorescence in 1852 which states that the wavelength of fluorescence emission is greater than that of the exciting radiation.  Richard Meyer then termed fluorophore in 1897 to describe a chemical group associated with fluorescence.  Since then, Fluorescein was created as a fluorescent dye by Adolph von Baeyer in 1871 and the method of staining was developed and utilized with the development of fluorescence microscopy in 1911.
Ethidium bromide and variants were developed in the 1950s, and in 1994, fluorescent proteins or FPs were introduced. Green fluorescent protein or GFP was discovered by Osamu Shimomura in the 1960s and was developed as a tracer molecule by Douglas Prasher in 1987.  FPs led to a breakthrough of live cell imaging with the ability to selectively tag genetic protein regions and observe protein functions and mechanisms. For this breakthrough, Shimomura was awarded the Nobel Prize in 2008.
New methods for tracking biomolecules have been developed including the use of colorimetric biosensors, photochromic compounds, biomaterials, and electrochemical sensors.  Fluorescent labeling is also a common method in which applications have expanded to enzymatic labeling, chemical labeling, protein labeling, and genetic labeling.