The methods that are currently used for studying receptor internalization primarily depend on the specific receptor under study and the tools available for that specific receptor. This chapter discusses the most common techniques used for assessing receptor internalization and downregulation in detail with reference to several studies applying these techniques. Receptor internalization is the process by which the receptor is removed from the cell surface and translocated into an intracellular compartment. Electron microscopy has been used in some studies of internalization of G protein-coupled receptors (GPCRs). The use of this technique has been limited, due mainly to the fact that the instrument is not easily accessible to most of the researchers in the field. Several different agents have been used to inhibit the internalization of cell surface receptors. Treatment with hypertonic medium such as sucrose has been shown to disrupt formation of clathrin coated pits. Internalization of several GPCRs has been shown to be clathrin mediated.