The opportunity to accurately localize radioactive substances in tissues at the cellular level became available with the introduction of relatively low energy beta-emitters, combined with the techniques of autoradiography. The major advantage offered by autoradiography is the ability to infer the location of individual molecules on the basis of the proximity of a reduced silver grain to this molecule. Therefore, attempts to increase the resolution of the method have utilized approaches that bring the two sites closer together. This paper will review some of the factors that relate to the theory and application of autoradiography when used with both light and electron microscopy.