Endocytosis involves the formation of internal membranes from the plasma membrane lipid bilayer through which plasma membrane lipids, proteins and extracellular fluid get internalized inside the cell. Since endocytosis not only controls the uptake of molecules, but also regulates signal transduction, cell adhesion, migration and development, it is not surprising that a misregulation in the trafficking cascade may lead to various diseases ranging from neuro-degeneration and diabetes to cancer. The key ways in which molecules can get into the cell are through Clathrin Mediated Endocytosis, Non Clathrin Mediated Endocytosis and through Macropinocytosis. In essence, all of these pathways show a convergent structure as they commence with invagination of the plasma membrane, advance through various endosomal compartments that end at the lysosomes. Where they differ is in the coat that will comprise the budding vesicle and the GTPase involved in the pinching off of the vesicle. Epidermal Growth Factor Receptor (EGFR) is a well-established and best characterized member of the Receptor Tyrosine Kinase family, which is known to be involved in various cellular processes ranging from signaling to growth and proliferation. It is well known that aberrant activity of this receptor is involved in pathogenesis of numerous forms of cancer. This review will describe the current knowledge concerning EGFR, regulation of its uptake through clathrin and dynamin dependent/ independent endocytic pathways, as well as the subsequent implications in numerous disorders associated with aberrant trafficking of the aforementioned receptor.